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There's not a day goes by that I don't see some variation of the theme that China is going to crash, or that somehow that nation will blindside us, and that its markets may fall 60%.
This is like saying the U.S. markets were in for a hard landing in March of 2009 after they had fallen more than 50%.
Folks who bit into this argument and bailed not only sold out at the worst possible moment, but then added agony to injury by sitting on the sidelines as the markets tore 95.68% higher over the next two years.
[ad#Google Adsense 336×280-IA]People forget that the U.S. stock market – as measured by the Dow Jones Industrial Average using weekly data – fell more than 89% from 1929 to 1932, more than 52% from 1937 to 1942, and more recently experienced a decline of more than 53% from 2008 to 2009 – and that doesn't even account for four 40+% declines beginning in 1901, 1906, 1916, and 1973.
Each was a great buying opportunity, and following those meltdowns, our markets rose more than 371% from 1929 to 1932, more than 222% from 1949 to 1956, more than 128% from 1937 to 1942, and more than 95.68% in just over two years starting in March 2009 – one of the fastest "melt-ups" in market history.
People forget that world markets dropped 40%-80% in 1987. And as legendary investor Jim Rogers noted earlier this month, that was not the end of the secular bull market in stocks, either.
People forget that our nation endured two world wars, a depression, multiple recessions, presidential assassinations, the near complete failure of our food belt, not to mention the deadliest terrorist attacks the world has ever seen, and more.
And guess what? It's still been the best place to invest for the last 100 years.
So what if China backs off or slows down?
The Asian currency markets blew up in 1997. Mexico's market fabulously went up in smoke during the great tequila crisis of 1994. And Argentina failed to the tune of a 76.9% crash starting in 1997 only to give way to a 1,724.56% rally from 2001 to 2011.
Gold rose by more than 600% in the 1970s, then fell by 50%, which terrified investors at the time. It subsequently rose by more than 850%, something else Mr. Rogers noted in recent interviews, as have I.
China is undoubtedly going to have several hard landings in our lifetime. Despite the fact that China is thousands of years old, modern China is a mere 40 years old, if you consider its opening following the historic Nixon-Kissinger visit in 1972.
And today's China has 1.3 billion people — all of whom want to live the way you do.
It's growing by an average of 9% a year or more and has done so every year for the last 41 years straight. We've just poured an estimated $7.7 trillion into our economy and the best we can do is 2.5%. The European Union (EU) is on track for 0.2% growth in 2012 after trillions in euro backing there.
Make no mistake: China's government is well aware that it has a problem. Unlike our own government and those in the EU, it has raised bank reserve requirements repeatedly before loosening them a bit last month. Beijing hiked interest rates six times in the last two years.
They are deliberately tapping on the brakes. They actually want segments of their economy to fail so they can reboot parts of the system, including China's real estate market, which is a prime example of this.
The Reality of Real Estate
Real estate has been bid up to obscene levels in many parts of the country – not throughout the entire country, but in parts. And those are the places Beijing wants real estate developers to fail so that values can come back to more realistic levels while capital gets freed up for additional investment.
Take Beijing for example. There are plenty of writers at the moment who love to point out that it will take the average Beijing resident 36 years to pay for their house versus 18 years in Singapore, 12 in New York, and 5 in Frankfurt.
Well, Beijing is a first-tier metropolis so right away you know this number isn't an apples to apples comparison. Factor in second- and third-tier cities like outside Beijing, Shanghai, Shenzhen, Guanzhou and prices drop to 3,000-5,000 RMB/m2 and take 4-10 years to pay back, which is roughly in line with international standards.
Look at cities like Moscow, Zurich, or Tokyo and the argument falls apart further.
For example, in Tokyo and other cities across Japan, Japanese banks at one point offered 100-year mortgages. And property, once acquired, tends to stay in the family for generations. You can still get 50-year mortgages if you want, and you might need to because property values remain unthinkably high even after a 30-year collapse.
Here are some other things to think about:
- Unlike the U.S. property bubble, which was nearly nationwide, Chinese borrowers must put 30% down for first-time purchases, 50% down on second purchases, and make full cash payments for third properties (where third properties are allowed). This means Chinese homeowners and banks can withstand a 30%-50% drawdown in prices before actually experiencing negative equity and stands in stark contrast to the United States, which is riding Occam's Razor in that regard.
- Using Beijing as an example for the entire Chinese housing market is shortsighted. While prices in second- and third-tier cities have also experienced increases in value, they are far less (relatively) than first-tier cities. And it is in second- and third-tier cities that the majority of Chinese citizens live. Using Beijing (or Shanghai) as a gauge for the entire Chinese real estate market would be like using Las Vegas, Miami, or Phoenix as a gauge of the entire U.S. property market in 2007.
- Chinese banks have not collateralized their mortgages into risky collateralized debt obligations (CDOs) and subsequently insured them with unregulated credit default swaps (CDS).
- And lastly, when the U.S. property bubble burst our country had more than $12 trillion of debt. China, by contrast, is sitting on $3.2 trillion in reserves (which represents 54.5% of the country's entire GDP). While Beijing would obviously rather not do it, it could theoretically recapitalize its entire banking sector and have plenty of money to spare.
More Than Manufacturing
Another doomsday scenario people like to bandy about is the notion that China will collapse if exports fail or U.S. demand drops. That's a gross exaggeration and much of the pabulum that you hear is completely wrong.
For example, it's commonly cited that exports make up approximately 40% or more of China's GDP. In reality, the figure is between 10%-20% even after decades of explosive growth. The CIA estimate is 18%, and of those exports, the U.S. accounts for a mere 18% of the total.
Fully 75% of the GDP comes from domestic spending and domestic investment.
As for the notion of U.S. demand, what China bashers don't realize is that the United States is dangerously close to being completely irrelevant to the Chinese growth model. China will not live and die by U.S. demand.
There is always going to be an imbalance between the value-added content of what China imports and what the country exports. China's exports are becoming more and more upscale just as Japan's did, which is probably the same pattern for all developing nations.
This is sort of like the great days of the British Empire – you sell us iron ore and we will sell you nails, hammers and shovels. If the value of an economy goes up, it's only natural that the value of the products it deals with, sells, and consumes will, too.
Also, China's trade surplus is shrinking as a percentage of gross domestic product (GDP), from almost 11% in 2007 to 3%-4% in 2010 to 0.246% ($14.5 billion) of its $5.87 trillion GDP as of November 2011 – further reinforcing the notion that domestic consumption is becoming a bigger force in China's economy even with the slowdown.
Don't Miss Out
I'm not saying China is going to have smooth sailing – but then again, neither did the U.S. in the 20th century, and the DJI gained 24,000% over that 100-year period. China is merely going through the first uncomfortable growing pains of its adolescence.
Remember, in 1912 the United States still used child labor, had massive inequalities of wealth, and women still couldn't vote. So holding China to the same standards as the modern United States is inappropriate, considering the country has only been open to the rest of the world for 40 years.
You have to look at China appropriately. You can't arbitrarily force the 21st century U.S. lens onto other countries in a vain effort to judge them.
Additionally, other parts of the Chinese economy are doing very well. Most manufacturing, agriculture, pollution treatment, water treatment, power, and resource development are just a few of the areas undergoing tremendous growth.
The point is, many people look down upon China with the same sort of derision once reserved for post-war Japan. And if you grew up in the 1950s or 1960s and thought Japan was only for cheap tin toys and didn't invest there, you missed out in the same way investors who look down their noses at China will.
Keep in mind that China's economy is roughly one-third the size of the overall U.S. economy and growing fast. Together America and the EU are approximately 10 times the size of China.
So if it does suffer a major correction, it's not the end of the world – nor the financial markets. And if the markets fall by 60% next year as some people suggest, I know what I'll be doing… buying.
Four Ways to Safely Invest in China
In the meantime, it's best to look at China within the overall scheme of things. And here are the investments you might want to consider:
- Buy yuan. It's still a blocked currency but you can legally get your hands on it using bank deposits, CDs, or exchange-traded funds (ETFs). The official story is that it's being held down. Bull. Since 2005 it's already risen by 23.29%, which is more than the U.S. government wants you to believe. If anything, the dollar is worth too much.
- Buy commodities. When China's markets grow, so too does global demand for raw materials. The nation has no choice but to buy because it doesn't have many native resources.
- Buy shares in Chinese companies on Chinese exchanges. One of the things that people miss in their rush to dismiss China is that they're tracking those shares of Chinese companies listed in the United States. That's a mistake. If the U.S. markets take a header, of course Chinese-listed companies on the NYSE and other U.S. exchanges will, too. Still, it's probably best to wait for the dust to settle before wading in.
- If you're aggressive, you can even try a classic "short" then go reverse long once the markets gain their footing.
— Keith Fitz-Gerald
[ad#jack p.s.]
Source: Money Morning


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Ben Gaines
Director of Product Management
Ben Gaines is a Director of Product Management for Adobe Analytics. In this role, he works closely with Adobe customers to understand their needs, provides input on product strategy and roadmap, and manages the planning and design of new features. Previously he has been a manager of digital analytics at ESPN, a Community Manager and Technical Writer at Adobe, and a Technical Support Engineer at Omniture prior to its acquisition by Adobe. Ben has an MBA from the University of Utah and a BA from Brigham Young University. He lives near Salt Lake City, Utah, with his wife and three children.

subset: commoncrawl


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Botshabelo Community and Village, Part 2. For more info, Click Here
I don't know why I'm not crying right now.
We just left Botshabelo for the second time. The donation bags hadn't arrived in time for our Sunday visit, so we returned today. We unpacked and sorted the clothes and medical supplies of the twenty or so fifty pound bags in a room about fifteen feet square. Each of us took one child at a time to pick out clothes. That meant there were usually about forty people in that one room, all digging through the once neat stacks of shirts and shoes, calling out and climbing over one another. It was chaos. I gained a deeper level of respect for Marion and Con Cloete after experiencing firsthand the difficulty of managing over two hundred kids. Unlike us, leaving exhausted after three hours, they live there.
When it came time to leave, I realized I had barely connected with anyone because I was so stressed about finding the right size of pants for boys who were happy just to get pants. I had no one to say teary goodbyes to, so I hugged kids I'd never met and left dry-eyed. Maybe my lack of tears is because I know I'll be back someday or maybe because I know they are in a happy, loving home. Maybe I just haven't realized I've left yet and soon I'll fall apart.
We returned to Botshabelo today. Various shipping errors delayed the bags full of supplies, so they were not available during our first visit. Additionally it gave us a good excuse to see the kids again. Alas, we pulled into the driveway and saw once again the place we so loved. The green and yellow sun-parched grass contrasted with the black, fire-scorched ground. Controlled burns seemed to be the preferred way of clearing fields in Joburg. We parked neatly on a small expanse of grass and the kids who had been eagerly awaiting our return started accumulating. We wasted no time hauling our duffel bags (full of medical supplies such as a defibrillator, various vitamins, and clothes) into a small convenient wooden house where we separated the clothes and prepared them for the kids. After they were all segmented into the appropriate sections by gender and size, we each took a kid in and dressed them in a top, pants, jacket, shoes, and a hat. If they were the right size, we labeled the clothes according to each child's designated number to ease the process of doing laundry for over two hundred children. After we had each dressed several kids, we moved on to the more independent teens and adults. The leftover baby clothes were given to the village mothers in the township's houses sprinkled around Botshabelo.
The kid that had taken a liking to me on our first trip to Botshabelo was definitely an interesting little dude. After a little pestering, he disclosed his name to me: "Moo" he said jokingly with a playful twinkle. He insisted fervently that it was his real name, but that might have been short for something or a nickname. He was eight and incredibly wise for his age. He was very observant and would constantly lead me around noticing things before me. He obviously lived very much in the moment and was not one to daydream and wander. He was one of minimal words, and that could have been because his English wasn't superb, or it could have been because he was careful to choose the most accurate ones. His sense of humor was also pretty dynamic and I enjoyed slaving around relentlessly, bolstering him with constant shoulder rides. One time I gave another kid a ride and immediately learned that I should not be unfaithful to him. Lesson learned. I thoroughly enjoyed spending time with him, and when we said goodbye for the second and final time, he let me hug him, a tremendous and precarious feat that no other person had accomplished. We said goodbye reluctantly and entered the bus mournfully.


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ACCURETIC- quinapril hydrochloride and hydrochlorothiazide tablet, film coated
Parke-Davis Div of Pfizer Inc
ACCURETIC is a fixed-combination tablet that combines an angiotensin-converting enzyme (ACE) inhibitor, quinapril hydrochloride, and a thiazide diuretic, hydrochlorothiazide.
Quinapril hydrochloride is chemically described as [3S-[2[R*(R*)], 3R*]]-2-[2-[[1-(ethoxycarbonyl)-3-phenylpropyl]amino]-1-oxopropyl]-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid, monohydrochloride. Its empirical formula is C25H30N2O5. HCl and its structural formula is:
Quinapril hydrochloride is a white to off-white amorphous powder that is freely soluble in aqueous solvents.
Hydrochlorothiazide is chemically described as: 6-Chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide. Its empirical formula is C7H8ClN3O4S2 and its structural formula is:
Hydrochlorothiazide is a white to off-white, crystalline powder which is slightly soluble in water but freely soluble in sodium hydroxide solution.
ACCURETIC is available for oral use as fixed combination tablets in three strengths of quinapril with hydrochlorothiazide: 10 mg (equivalent to 10.832 mg Quinapril Hydrochloride) with 12.5 mg (ACCURETIC 10/12.5), 20 mg (equivalent to 21.664 mg Quinapril Hydrochloride) with 12.5 mg (ACCURETIC 20/12.5), and 20 mg (equivalent to 21.664 mg Quinapril Hydrochloride) with 25 mg (ACCURETIC 20/25). Inactive ingredients: candelilla wax, crospovidone, hydroxypropyl cellulose, hypromellose, iron oxide red, iron oxide yellow, lactose, magnesium carbonate, magnesium stearate, polyethylene glycol, povidone, and titanium dioxide.
The principal metabolite of quinapril, quinaprilat, is an inhibitor of ACE activity in human subjects and animals. ACE is peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor, angiotensin II. The effect of quinapril in hypertension appears to result primarily from the inhibition of circulating and tissue ACE activity, thereby reducing angiotensin II formation. Quinapril inhibits the elevation in blood pressure caused by intravenously administered angiotensin I, but has no effect on the pressor response to angiotensin II, norepinephrine, or epinephrine. Angiotensin II also stimulates the secretion of aldosterone from the adrenal cortex, thereby facilitating renal sodium and fluid reabsorption. Reduced aldosterone secretion by quinapril may result in a small increase in serum potassium. In controlled hypertension trials, treatment with quinapril alone resulted in mean increases in potassium of 0.07 mmol/L (see PRECAUTIONS). Removal of angiotensin II negative feedback on renin secretion leads to increased plasma renin activity (PRA).
While the principal mechanism of antihypertensive effect is thought to be through the renin-angiotensin-aldosterone system, quinapril exerts antihypertensive actions even in patients with low renin hypertension. Quinapril was an effective antihypertensive in all races studied, although it was somewhat less effective in blacks (usually a predominantly low renin group) than in non-blacks. ACE is identical to kininase II, an enzyme that degrades bradykinin, a potent peptide vasodilator; whether increased levels of bradykinin play a role in the therapeutic effect of quinapril remains to be elucidated.
Hydrochlorothiazide is a thiazide diuretic. Thiazides affect the renal tubular mechanisms of electrolyte reabsorption, directly increasing excretion of sodium and chloride in approximately equivalent amounts. Indirectly, the diuretic action of hydrochlorothiazide reduces plasma volume, with consequent increases in plasma renin activity, increases in aldosterone secretion, increases in urinary potassium loss, and decreases in serum potassium. The renin-aldolsterone link is mediated by angiotensin, so coadministration of an ACE inhibitor tends to reverse the potassium loss associated with these diuretics.
The mechanism of the antihypertensive effect of thiazides is unknown.
The rate and extent of absorption of quinapril and hydrochlorothiazide from ACCURETIC tablets are not different, respectively, from the rate and extent of absorption of quinapril and hydrochlorothiazide from immediate-release monotherapy formulations, either administered concurrently or separately. Following oral administration of Accupril (quinapril monotherapy) tablets, peak plasma quinapril concentrations are observed within 1 hour. Based on recovery of quinapril and its metabolites in urine, the extent of absorption is at least 60%. The absorption of hydrochlorothiazide is somewhat slower (1 to 2.5 hours) and more complete (50% to 80%).
The rate of quinapril absorption was reduced by 14% when ACCURETIC tablets were administered with a high-fat meal as compared to fasting, while the extent of absorption was not affected. The rate of hydrochlorothiazide absorption was reduced by 12% when ACCURETIC tablets were administered with a high-fat meal, while the extent of absorption was not significantly affected. Therefore, ACCURETIC may be administered without regard to food.
Following absorption, quinapril is deesterified to its major active metabolite, quinaprilat (about 38% of oral dose), and to other minor inactive metabolites. Following multiple oral dosing of quinapril, there is an effective accumulation half-life of quinaprilat of approximately 3 hours, and peak plasma quinaprilat concentrations are observed approximately 2 hours postdose. Approximately 97% of either quinapril or quinaprilat circulating in plasma is bound to proteins. Hydrochlorothiazide is not metabolized. Its apparent volume of distribution is 3.6 to 7.8 L/kg, consistent with measured plasma protein binding of 67.9%. The drug also accumulates in red blood cells, so that whole blood levels are 1.6 to 1.8 times those measured in plasma.
Some placental passage occurred when quinapril was administered to pregnant rats. Studies in rats indicate that quinapril and its metabolites do not cross the blood-brain barrier. Hydrochlorothiazide crosses the placenta freely but not the blood-brain barrier.
Quinaprilat is eliminated primarily by renal excretion, up to 96% of an IV dose, and has an elimination half-life in plasma of approximately 2 hours and a prolonged terminal phase with a half-life of 25 hours. Hydrochlorothiazide is excreted unchanged by the kidney. When plasma levels have been followed for at least 24 hours, the plasma half-life has been observed to vary between 4 to 15 hours. At least 61% of the oral dose is eliminated unchanged within 24 hours.
In patients with renal insufficiency, the elimination half-life of quinaprilat increases as creatinine clearance decreases. There is a linear correlation between plasma quinaprilat clearance and creatinine clearance. In patients with end-stage renal disease, chronic hemodialysis or continuous ambulatory peritoneal dialysis have little effect on the elimination of quinapril and quinaprilat. Elimination of quinaprilat is reduced in elderly patients (≥65 years) and in those with heart failure; this reduction is attributable to decrease in renal function (see DOSAGE AND ADMINISTRATION). Quinaprilat concentrations are reduced in patients with alcoholic cirrhosis due to impaired deesterification of quinapril. In a study of patients with impaired renal function (mean creatinine clearance of 19 mL/min), the half-life of hydrochlorothiazide elimination was lengthened to 21 hours.
The pharmacokinetics of quinapril and quinaprilat are linear over a single-dose range of 5- to 80-mg doses and 40- to 160-mg in multiple daily doses.
Single doses of 20 mg of quinapril provide over 80% inhibition of plasma ACE for 24 hours. Inhibition of the pressor response to angiotensin I is shorter-lived, with a 20-mg dose giving 75% inhibition for about 4 hours, 50% inhibition for about 8 hours, and 20% inhibition at 24 hours. With chronic dosing, however, there is substantial inhibition of angiotensin II levels at 24 hours by doses of 20 to 80 mg.
Administration of 10 to 80 mg of quinapril to patients with mild to severe hypertension results in a reduction of sitting and standing blood pressure to about the same extent with minimal effect on heart rate. Symptomatic postural hypotension is infrequent, although it can occur in patients who are salt- and/or volume-depleted (see WARNINGS).
Antihypertensive activity commences within 1 hour with peak effects usually achieved by 2 to 4 hours after dosing. During chronic therapy, most of the blood pressure lowering effect of a given dose is obtained in 1 to 2 weeks. In multiple-dose studies, 10 to 80 mg per day in single or divided doses lowered systolic and diastolic blood pressure throughout the dosing interval, with a trough effect of about 5 to 11/3 to 7 mm Hg. The trough effect represents about 50% of the peak effect.
While the dose-response relationship is relatively flat, doses of 40 to 80 mg were somewhat more effective at trough than 10 to 20 mg, and twice-daily dosing tended to give a somewhat lower trough blood pressure than once-daily dosing with the same total dose. The antihypertensive effect of quinapril continues during long-term therapy, with no evidence of loss of effectiveness.
Hemodynamic assessments in patients with hypertension indicate that blood pressure reduction produced by quinapril is accompanied by a reduction in total peripheral resistance and renal vascular resistance with little or no change in heart rate, cardiac index, renal blood flow, glomerular filtration rate, or filtration fraction.
Therapeutic effects of quinapril appear to be the same for elderly (≥65 years of age) and younger adult patients given the same daily dosages, with no increase in adverse events in elderly patients. In patients with hypertension, quinapril 10 to 40 mg was similar in effectiveness to captopril, enalapril, propranolol, and thiazide diuretics.
After oral administration of hydrochlorothiazide, diuresis begins within 2 hours, peaks in about 4 hours, and lasts about 6 to 12 hours. Use of quinapril with a thiazide diuretic gives blood pressure lowering effect greater than that seen with either agent alone. In clinical trials of quinapril/hydrochlorothiazide using quinapril doses of 2.5 to 40 mg and hydrochlorothiazide doses of 6.25 to 25 mg, the antihypertensive effects were sustained for at least 24 hours, and increased with increasing dose of either component. Although quinapril monotherapy is somewhat less effective in blacks than in non-blacks, the efficacy of combination therapy appears to be independent of race. By blocking the renin-angiotensin-aldosterone axis, administration of quinapril tends to reduce the potassium loss associated with the diuretic. In clinical trials of ACCURETIC, the average change in serum potassium was near zero when 2.5 to 40 mg of quinapril was combined with hydrochlorothiazide 6.25 mg, and the average subject who received 10 to 20/12.5 to 25 mg experienced a milder reduction in serum potassium than that experienced by the average subject receiving the same dose of hydrochlorothiazide monotherapy.
ACCURETIC is indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including the class to which this drug principally belongs. There are no controlled trials demonstrating risk reduction with ACCURETIC.
Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program's Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC).
Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly.
Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal.
Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy.
This fixed combination is not indicated for the initial therapy of hypertension (see DOSAGE AND ADMINISTRATION).
In using ACCURETIC, consideration should be given to the fact that another angiotensin-converting enzyme inhibitor, captopril, has caused agranulocytosis, particularly in patients with renal impairment or collagen-vascular disease. Available data are insufficient to show that quinapril does not have a similar risk (see WARNINGS: Neutropenia/Agranulocytosis).
Black patients receiving ACE inhibitor monotherapy have been reported to have a higher incidence of angioedema compared to non-blacks. It should also be noted that in controlled clinical trials, ACE inhibitors have an effect on blood pressure that is less in black patients than in non-blacks.
ACCURETIC is contraindicated in patients who are hypersensitive to quinapril or hydrochlorothiazide and in patients with a history of angioedema related to previous treatment with an ACE inhibitor.
ACCURETIC is contraindicated in combination with a neprilysin inhibitor (e.g., sacubitril). Do not administer ACCURETIC within 36 hours of switching to or from sacubitril/valsartan, a neprilysin inhibitor (see WARNINGS and PRECAUTIONS).
Because of the hydrochlorothiazide components, this product is contraindicated in patients with anuria or hypersensitivity to other sulfonamide-derived drugs.
Do not co-administer ACCURETIC with aliskiren:
Presumably because angiotensin converting inhibitors affect the metabolism of eicosanoids and polypeptides, including endogenous bradykinin, patients receiving ACE inhibitors (including quinapril) may be subject to a variety of adverse reactions, some of them serious.
Angioedema of the face, extremities, lips, tongue, glottis, and larynx has been reported in patients treated with ACE inhibitors and has been seen in 0.1% of patients receiving quinapril. In two similarly sized US postmarketing quinapril trials that, combined, enrolled over 3,000 black patients and over 19,000 non-blacks, angioedema was reported in 0.30% and 0.55% of blacks (in Study 1 and 2, respectively) and 0.39% and 0.17% of non-blacks. Angioedema associated with laryngeal edema can be fatal. If laryngeal stridor or angioedema of the face, tongue, or glottis occurs, treatment with ACCURETIC should be discontinued immediately, the patient treated in accordance with accepted medical care, and carefully observed until the swelling disappears. In instances where swelling is confined to the face and lips, the condition generally resolves without treatment; antihistamines may be useful in relieving symptoms. Where there is involvement of the tongue, glottis, or larynx likely to cause airway obstruction, emergency therapy including, but not limited to, subcutaneous epinephrine solution 1:1000 (0.3 to 0.5 mL) should be promptly administered (see PRECAUTIONS and ADVERSE REACTIONS).
Patients taking concomitant mammalian target of rapamycin (mTOR inhibitor) (e.g., temsirolimus) therapy or a neprilysin inhibitor may be at increased risk for angioedema.
Intestinal angioedema has been reported in patients treated with ACE inhibitors. These patients presented with abdominal pain (with or without nausea or vomiting); in some cases there was no prior history of facial angioedema and C-1 esterase levels were normal. The angioedema was diagnosed by procedures including abdominal CT scan or ultrasound, or at surgery, and symptoms resolved after stopping the ACE inhibitor. Intestinal angioedema should be included in the differential diagnosis of patients on ACE inhibitors presenting with abdominal pain.
Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk of angioedema while receiving an ACE inhibitor (see also CONTRAINDICATIONS).
Two patients undergoing desensitizing treatment with Hymenoptera venom while receiving ACE inhibitors sustained life-threatening anaphylactoid reactions. In the same patients, these reactions were avoided when ACE inhibitors were temporarily withheld, but they reappeared upon inadvertent challenge.
Anaphylactoid reactions have been reported in patients dialyzed with high-flux membranes and treated concomitantly with an ACE inhibitor. Anaphylactoid reactions have also been reported in patients undergoing low-density lipoprotein apheresis with dextran sulfate absorption.
Rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant hepatic necrosis and (sometimes) death. The mechanism of this syndrome is not understood. Patients receiving ACE inhibitors who develop jaundice or marked elevations of hepatic enzymes should discontinue the ACE inhibitor and receive appropriate medical follow-up.
ACCURETIC can cause symptomatic hypotension, probably not more frequently than either monotherapy. It was reported in 1.2% of 1,571 patients receiving ACCURETIC during clinical trials. Like other ACE inhibitors, quinapril has been only rarely associated with hypotension in uncomplicated hypertensive patients.
Symptomatic hypotension sometimes associated with oliguria and/or progressive azotemia, and rarely acute renal failure and/or death, include patients with the following conditions or characteristics: heart failure, hyponatremia, high dose diuretic therapy, recent intensive diuresis or increase in diuretic dose, renal dialysis or severe volume and/or salt depletion of any etiology. Volume and/or salt depletion should be corrected before initiating therapy with ACCURETIC.
ACCURETIC should be used cautiously in patients receiving concomitant therapy with other antihypertensives. The thiazide component of ACCURETIC may potentiate the action of other antihypertensive drugs, especially ganglionic or peripheral adrenergic-blocking drugs. The antihypertensive effects of the thiazide component may also be enhanced in the postsympathectomy patients.
In patients at risk of excessive hypotension, therapy with ACCURETIC should be started under close medical supervision. Such patients should be followed closely for the first 2 weeks of treatment and whenever the dosage of quinapril or diuretic is increased. Similar considerations may apply to patients with ischemic heart or cerebrovascular disease in whom an excessive fall in blood pressure could result in myocardial infarction or cerebrovascular accident.
If excessive hypotension occurs, the patient should be placed in a supine position and, if necessary, treated with intravenous infusion of normal saline. ACCURETIC treatment usually can be continued following restoration of blood pressure and volume. If symptomatic hypotension develops, a dose reduction or discontinuation of ACCURETIC may be necessary.
ACCURETIC should be used with caution in patients with severe renal disease. Thiazides may precipitate azotemia in such patients, and the effects of repeated dosing may be cumulative.
When the renin-angiotensin-aldosterone system is inhibited by quinapril, changes in renal function may be anticipated in susceptible individuals. In patients with severe congestive heart failure, whose renal function may depend on the activity of the renin-angiotensin-aldosterone system, treatment with angiotensin-converting enzyme inhibitors (including quinapril) may be associated with oliguria and/or progressive azotemia and (rarely) with acute renal failure and/or death.
In clinical studies in hypertensive patients with unilateral renal artery stenosis, treatment with ACE inhibitors was associated with increases in blood urea nitrogen and serum creatinine; these increases were reversible upon discontinuation of ACE inhibitor, concomitant diuretic, or both. When such patients are treated with ACCURETIC, renal function should be monitored during the first few weeks of therapy.
Some quinapril-treated hypertensive patients with no apparent preexisting renal vascular diseases have developed increases in blood urea nitrogen and serum creatinine, usually minor and transient, especially when quinapril has been given concomitantly with a diuretic. This is more likely to occur in patients with pre-existing renal impairment. Dosage reduction of ACCURETIC may be required. Evaluation of the hypertensive patients should also include assessment of the renal function (see DOSAGE AND ADMINISTRATION).
Another ACE inhibitor, captopril, has been shown to cause agranulocytosis and bone marrow depression rarely in patients with uncomplicated hypertension, but more frequently in patients with renal impairment, especially if they also have a collagen vascular disease, such as systemic lupus erythematosus or scleroderma. Agranulocytosis did occur during quinapril treatment in one patient with a history of neutropenia during previous captopril therapy. Available data from clinical trials of quinapril are insufficient to show that, in patients without prior reactions to other ACE inhibitors, quinapril does not cause agranulocytosis at similar rates. As with other ACE inhibitors, periodic monitoring of white blood cell counts in patients with collagen vascular disease and/or renal disease should be considered.
Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue ACCURETIC as soon as possible. These adverse outcomes are usually associated with use of these drugs in the second and third trimester of pregnancy. Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. Appropriate management of maternal hypertension during pregnancy is important to optimize outcomes for both mother and fetus.
In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus. Perform serial ultrasound examinations to assess the intra-amniotic environment. If oligohydramnios is observed, discontinue ACCURETIC, unless it is considered life-saving for the mother. Fetal testing may be appropriate, based on the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Closely observe infants with histories of in utero exposure to ACCURETIC for hypotension, oliguria, and hyperkalemia (see PRECAUTIONS, Pediatric Use).
Intrauterine exposure to thiazide diuretics is associated with fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions that occurred in adults.
No teratogenic effects of quinapril were seen in studies of pregnant rats and rabbits. On a mg/kg basis, the doses used were up to 180 times (in rats) and one time (in rabbits) the maximum recommended human dose. No teratogenic effects of ACCURETIC were seen in studies of pregnant rats and rabbits. On a mg/kg (quinapril/hydrochlorothiazide) basis, the doses used were up to 188/94 times (in rats) and 0.6/0.3 times (in rabbits) the maximum recommended human dose.
ACCURETIC should be used with caution in patients with impaired hepatic function or progressive liver disease, since minor alterations of fluid and electrolyte balance may precipitate hepatic coma. Also, since the metabolism of quinapril to quinaprilat is normally dependent upon hepatic esterases, patients with impaired liver function could develop markedly elevated plasma levels of quinapril. No normal pharmacokinetic studies have been carried out in hypertensive patients with impaired liver function.
Thiazide diuretics have been reported to cause exacerbation or activation of systemic lupus erythematosus.
Hydrochlorothiazide, a sulfonamide, can cause an idiosyncratic reaction, resulting in acute angle-closure glaucoma and elevated intraocular pressure with or without a noticeable acute myopic shift and/or choroidal effusions. Symptoms may include acute onset of decreased visual acuity or ocular pain and typically occur within hours to weeks of drug initiation. Untreated, the angle-closure glaucoma may result in permanent visual field loss. The primary treatment is to discontinue hydrochlorothiazide as rapidly as possible. Prompt medical or surgical treatments may need to be considered if the intraocular pressure remains uncontrolled. Risk factors for developing acute angle-closure glaucoma may include a history of sulfonamide or penicillin allergy.
In clinical trials, hyperkalemia (serum potassium ≥5.8 mmol/L) occurred in approximately 2% of patients receiving quinapril. In most cases, elevated serum potassium levels were isolated values which resolved despite continued therapy. Less than 0.1% of patients discontinued therapy due to hyperkalemia. Risk factors for the development of hyperkalemia include renal insufficiency, diabetes mellitus, and the concomitant use of other drugs that raise serum potassium levels.
Hydrochlorothiazide can cause hypokalemia and hyponatremia. Hypomagnesemia can result in hypokalemia which appears difficult to treat despite potassium repletion. Drugs that inhibit the renin-angiotensin system can cause hyperkalemia. The risk of hyperkalemia may be increased in patients with renal insufficiency, diabetes mellitus or with concomitant use of drugs that raise serum potassium (see Drug Interactions). The risk of hypokalemia may be increased in patients with cirrhosis, brisk diuresis, or with concomitant use of drugs that lower serum potassium. Monitor serum electrolytes periodically.
Hydrochlorothiazide may alter glucose tolerance and raise serum levels of cholesterol and triglycerides.
Hydrochlorothiazide may raise the serum uric acid level due to reduced clearance of uric acid and may cause or exacerbate hyperuricemia and precipitate gout in susceptible patients.
Hydrochlorothiazide decreases urinary calcium excretion and may cause elevations of serum calcium. Monitor calcium levels in patients with hypercalcemia receiving ACCURETIC.
Presumably due to the inhibition of the degradation of endogenous bradykinin, persistent nonproductive cough has been reported with all ACE inhibitors, resolving after discontinuation of therapy. ACE inhibitor-induced cough should be considered in the differential diagnosis of cough.
In patients undergoing surgery or during anesthesia with agents that produce hypotension, quinapril will block the angiotensin II formation that could otherwise occur secondary to compensatory renin release. Hypotension that occurs as a result of this mechanism can be corrected by volume expansion.
Angioedema, including laryngeal edema, can occur with treatment with ACE inhibitors, especially following the first dose. Tell patients receiving ACCURETIC to immediately report any signs or symptoms suggesting angioedema (swelling of face, eyes, lips, or tongue, or difficulty in breathing) and to temporarily discontinue Accuretic until after consulting with the prescribing physician.
Tell female patients of childbearing age about the consequences of exposure to ACCURETIC during pregnancy. Discuss treatment options with women planning to become pregnant. Ask patients to report pregnancies to their physicians as soon as possible.
Tell patients receiving ACCURETIC that lightheadedness can occur, especially during the first days of therapy, and to report it to the prescribing physician. Tell the patient if syncope occurs, discontinue ACCURETIC until the physician has been consulted.
Tell patients that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to an excessive fall in blood pressure because of reduction in fluid volume, with the same consequences of lightheadedness and possible syncope.
Tell patients planning to undergo major surgery and/ or general or spinal anesthesia to inform their physicians that they are taking an ACE inhibitor.
Tell patients receiving ACCURETIC not to use potassium supplements or salt substitutes containing potassium without consulting the prescribing physician.
Tell patients to promptly report any indication of infection (e.g., sore throat, fever) which could be a sign of neutropenia.
Instruct patients taking hydrochlorothiazide to protect skin from the sun and undergo regular skin cancer screening.
NOTE: As with many other drugs, certain advice to patients being treated with quinapril is warranted. This information is intended to aid in the safe and effective use of this medication. It is not a disclosure of all possible adverse or intended effects.
The hydrochlorothiazide component of ACCURETIC may decrease serum PBI levels without signs of thyroid disturbance.
Therapy with ACCURETIC should be interrupted for a few days before carrying out tests of parathyroid function.
Coadministration of ACCURETIC with other drugs that raise serum potassium levels may result in hyperkalemia. Monitor serum potassium in such patients.
Increased serum lithium levels and symptoms of lithium toxicity have been reported in patients receiving ACE inhibitors during therapy with lithium. Because renal clearance of lithium is reduced by thiazides, the risk of lithium toxicity is presumably raised further when, as in therapy with ACCURETIC, a thiazide diuretic is coadministered with the ACE inhibitor. ACCURETIC and lithium should be coadministered with caution, and frequent monitoring of serum lithium levels is recommended.
Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. Most patients receiving the combination of two RAS inhibitors do not obtain any additional benefit compared to monotherapy. In general, avoid combined use of RAS inhibitors. Closely monitor blood pressure, renal function and electrolytes in patients on ACCURETIC and other agents that affect the RAS.
Do not co-administer aliskiren with ACCURETIC in patients with diabetes. Avoid concomitant use of aliskiren with ACCURETIC in patients with renal impairment (GFR <60 mL/min/1.73 m2).
Simultaneous administration of tetracycline with quinapril reduced the absorption of tetracycline by approximately 28% to 37%, possibly due to the high magnesium content in quinapril tablets. This interaction should be considered if coprescribing quinapril and tetracycline or other drugs that interact with magnesium.
Nitritoid reactions (symptoms include facial flushing, nausea, vomiting, and hypotension) have been reported rarely in patients on therapy with injectable gold (sodium aurothiomalate) and concomitant ACE inhibitor therapy.
In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, co-administration of NSAIDs, including selective COX-2 inhibitors, with ACE inhibitors, including quinapril, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving quinapril and NSAID therapy.
The antihypertensive effect of ACE inhibitors, including quinapril may be attenuated by NSAIDs.
Patients taking concomitant mTOR inhibitor (e.g., temsirolimus) therapy or a neprilysin inhibitor may be at increased risk for angioedema.
Drug interaction studies of quinapril and other agents showed:
When administered concurrently, the following drugs may interact with thiazide diuretics.
Carcinogenicity, mutagenicity, and fertility studies have not been conducted in animals with ACCURETIC.
Quinapril hydrochloride was not carcinogenic in mice or rats when given in doses up to 75 or 100 mg/kg/day (50 or 60 times the maximum human daily dose, respectively, on a mg/kg basis and 3.8 or 10 times the maximum human daily dose on a mg/m2 basis) for 104 weeks. Female rats given the highest dose level had an increased incidence of mesenteric lymph node hemangiomas and skin/subcutaneous lipomas. Neither quinapril nor quinaprilat were mutagenic in the Ames bacterial assay with or without metabolic activation. Quinapril was also negative in the following genetic toxicology studies: in vitro mammalian cell point mutation, sister chromatid exchange in cultured mammalian cells, micronucleus test with mice, in vitro chromosome aberration with V79 cultured lung cells, and in an in vivo cytogenetic study with rat bone marrow. There were no adverse effects on fertility or reproduction in rats at doses up to 100 mg/kg/day (60 and 10 times the maximum daily human dose when based on mg/kg and mg/m2, respectively).
Under the auspices of the National Toxicology Program, rats and mice received hydrochlorothiazide in their feed for 2 years, at doses up to 600 mg/kg/day in mice and up to 100 mg/kg/day in rats. These studies uncovered no evidence of a carcinogenic potential of hydrochlorothiazide in rats or female mice, but there was "equivocal" evidence of hepatocarcinogenicity in male mice. Hydrochlorothiazide was not genotoxic in in vitro assays using strains TA 98, TA 100, TA 1535, TA 1537, and TA 1538 of Salmonella typhimurium (the Ames test); in the Chinese hamster ovary (CHO) test for chromosomal aberrations; or in vivo assays using mouse germinal cell chromosomes, Chinese hamster bone marrow chromosomes, and the Drosophila sex-linked recessive lethal trait gene. Positive test results were obtained in the in vitro CHO sister chromatid exchange (clastogenicity) test and in the mouse lymphoma cell (mutagenicity) assays, using concentrations of hydrochlorothiazide of 43 to 1300 µg/mL. Positive test results were also obtained in the Aspergillus nidulans nondisjunction assay, using an unspecified concentration of hydrochlorothiazide.
Hydrochlorothiazide had no adverse effects on the fertility of mice and rats of either sex in studies wherein these species were exposed, via their diets, to doses of up to 100 and 4 mg/kg/day, respectively, prior to mating and throughout gestation.
Because quinapril and hydrochlorothiazide are secreted in human milk, caution should be exercised when ACCURETIC is administered to a nursing woman.
Because of the potential for serious adverse reactions in nursing infants from hydrochlorothiazide and the unknown effects of quinapril in infants, a decision should be made whether to discontinue nursing or to discontinue ACCURETIC, taking into account the importance of the drug to the mother.
Clinical studies of quinapril HCl/hydrochlorothiazide did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
If oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function. Removal of quinapril, which crosses the placenta, from the neonatal circulation is not significantly accelerated by these means.
Safety and effectiveness of ACCURETIC in children have not been established.
ACCURETIC has been evaluated for safety in 1571 patients in controlled and uncontrolled studies. Of these, 498 were given quinapril plus hydrochlorothiazide for at least 1 year, with 153 patients extending combination therapy for over 2 years. In clinical trials with ACCURETIC, no adverse experience specific to the combination has been observed. Adverse experiences that have occurred have been limited to those that have been previously reported with quinapril or hydrochlorothiazide.
Adverse experiences were usually mild and transient, and there was no relationship between side effects and age, sex, race, or duration of therapy. Discontinuation of therapy because of adverse effects was required in 2.1% in patients in controlled studies. The most common reasons for discontinuation of therapy with ACCURETIC were cough (1.0%; see PRECAUTIONS) and headache (0.7%).
Adverse experiences probably or possibly related to therapy or of unknown relationship to therapy occurring in 1% or more of the 943 patients treated with quinapril plus hydrochlorothiazide in controlled trials are shown below.
Percent of Patients in Controlled Trials | ||
Quinapril/HCTZ N = 943 | Placebo N = 100 |
Headache |
6.7 |
30.0 |
Dizziness |
4.8 |
4.0 |
Coughing |
3.2 |
2.0 |
Fatigue |
2.9 |
3.0 |
Myalgia |
2.4 |
5.0 |
Viral Infection |
1.9 |
4.0 |
Rhinitis |
2.0 |
3.0 |
Nausea and/or Vomiting |
1.8 |
6.0 |
Abdominal Pain |
1.7 |
4.0 |
Back Pain |
1.5 |
2.0 |
Diarrhea |
1.4 |
1.0 |
Upper Respiratory Infection |
1.3 |
4.0 |
Insomnia |
1.2 |
2.0 |
Somnolence |
1.2 |
0.0 |
Bronchitis |
1.2 |
1.0 |
Dyspepsia |
1.2 |
2.0 |
Asthenia |
1.1 |
1.0 |
Pharyngitis |
1.1 |
2.0 |
Vasodilatation |
1.0 |
1.0 |
Vertigo |
1.0 |
2.0 |
Chest Pain |
1.0 |
2.0 |
Clinical adverse experiences probably, possibly, or definitely related or of uncertain relationship to therapy occurring in ≥0.5% to <1.0% (except as noted) of the patients treated with quinapril/HCTZ in controlled and uncontrolled trials (N=1571) and less frequent, clinically significant events seen in clinical trials or postmarketing experience (the rarer events are in italics) include (listed by body system):
Asthenia, Malaise |
Palpitation, Tachycardia, Heart Failure, Hyperkalemia, Myocardial Infarction, Cerebrovascular Accident, Hypertensive Crisis, Angina Pectoris, Orthostatic Hypotension, Cardiac Rhythm Disturbance |
Mouth or Throat Dry, Gastrointestinal Hemorrhage, Pancreatitis, Abnormal Liver Function Tests |
Nervousness, Vertigo, Paresthesia |
Sinusitis, Dyspnea |
Pruritus, Sweating Increased, Erythema Multiforme, Exfoliative Dermatitis, Photosensitivity Reaction, Alopecia, Pemphigus |
Acute Renal Failure, Impotence |
Agranulocytosis, Thrombocytopenia, Arthralgia |
Angioedema: |
Angioedema has been reported in 0.1% of patients receiving quinapril (0.1%) (see WARNINGS). |
The following serious nonfatal adverse events, regardless of their relationship to quinapril and HCTZ combination tablets, have been reported during extensive postmarketing experience:
Non-melanoma Skin Cancer: Hydrochlorothiazide is associated with an increased risk of non-melanoma skin cancer. In a study conducted in the Sentinel System, increased risk was predominantly for squamous cell carcinoma (SCC) and in white patients taking large cumulative doses. The increased risk for SCC in the overall population was approximately 1 additional case per 16,000 patients per year, and for white patients taking a cumulative dose of ≥50,000 mg the risk increase was approximately 1 additional SCC case for every 6,700 patients per year.
BODY AS A WHOLE: Shock, accidental injury, neoplasm, cellulitis, ascites, generalized edema, hernia and anaphylactoid reaction.
CARDIOVASCULAR SYSTEM: Bradycardia, cor pulmonale, vasculitis, and deep vein thrombosis.
DIGESTIVE SYSTEM: Gastrointestinal carcinoma, cholestatic jaundice, hepatitis, esophagitis, vomiting, and diarrhea.
EYE DISORDERS: Acute myopia and acute angle closure glaucoma (see WARNINGS).
HEMIC SYSTEM: Anemia.
METABOLIC AND NUTRITIONAL DISORDERS: Weight loss.
MUSCULOSKELETAL SYSTEM: Myopathy, myositis, and arthritis.
NERVOUS SYSTEM: Paralysis, hemiplegia, speech disorder, abnormal gait, meningism, and amnesia.
RESPIRATORY SYSTEM: Pneumonia, asthma, respiratory infiltration, and lung disorder.
SKIN AND APPENDAGES: Urticaria, macropapular rash, and petechiases.
SPECIAL SENSES: Abnormal vision.
UROGENITAL SYSTEM: Kidney function abnormal, albuminuria, pyuria, hematuria, and nephrosis.
Quinapril monotherapy has been evaluated for safety in 4960 patients. In clinical trials adverse events which occurred with quinapril were also seen with ACCURETIC. In addition, the following were reported for quinapril at an incidence >0.5%: depression, back pain, constipation, syncope, and amblyopia.
Hydrochlorothiazide has been extensively prescribed for many years, but there has not been enough systematic collection of data to support an estimate of the frequency of the observed adverse reactions. Within organ-system groups, the reported reactions are listed here in decreasing order of severity, without regard to frequency.
Weakness. |
Orthostatic hypotension (may be potentiated by alcohol, barbiturates, or narcotics). |
Pancreatitis, jaundice (intrahepatic cholestatic), sialadenitis, vomiting, diarrhea, cramping, nausea, gastric irritation, constipation, and anorexia. |
Vertigo, lightheadedness, transient blurred vision, headache, paresthesia, xanthopsia, weakness, and restlessness. |
Muscle spasm. |
Aplastic anemia, agranulocytosis, leukopenia, thrombocytopenia, and hemolytic anemia. |
Renal failure, renal dysfunction, interstitial nephritis (see WARNINGS). |
Hyperglycemia, glycosuria, and hyperuricemia. |
Necrotizing angiitis, Stevens-Johnson syndrome, respiratory distress (including pneumonitis and pulmonary edema), purpura, urticaria, rash, and photosensitivity. |
Increases (>1.25 times the upper limit of normal) in serum creatinine and blood urea nitrogen were observed in 3% and 4%, respectively, of patients treated with ACCURETIC. Most increases were minor and reversible, which can occur in patients with essential hypertension but most frequently in patients with renal artery stenosis (see PRECAUTIONS).
Other clinically important changes in standard laboratory tests were rarely associated with ACCURETIC administration. Elevations in uric acid, glucose, magnesium, cholesterol, triglyceride, and calcium (see PRECAUTIONS) have been reported.
No specific information is available on the treatment of overdosage with ACCURETIC or quinapril monotherapy; treatment should be symptomatic and supportive. Therapy with ACCURETIC should be discontinued, and the patient should be observed. Dehydration, electrolyte imbalance, and hypotension should be treated by established procedures.
The oral median lethal dose of quinapril/hydrochlorothiazide in combination ranges from 1063/664 to 4640/2896 mg/kg in mice and rats. Doses of 1440 to 4280 mg/kg of quinapril cause significant lethality in mice and rats. In single-dose studies of hydrochlorothiazide, most rats survived doses up to 2.75 g/kg.
Data from human overdoses of ACE inhibitors are scanty; the most likely manifestation of human quinapril overdosage is hypotension. In human hydrochlorothiazide overdose, the most common signs and symptoms observed have been those of dehydration and electrolyte depletion (hypokalemia, hypochloremia, hyponatremia). If digitalis has also been administered, hypokalemia may accentuate cardiac arrhythmias.
Laboratory determinations of serum levels of quinapril and its metabolites are not widely available, and such determinations have, in any event, no established role in the management of quinapril overdose.
No data are available to suggest physiological maneuvers (e.g., maneuvers to change the pH of the urine) that might accelerate elimination of quinapril and its metabolites. Hemodialysis and peritoneal dialysis have little effect on the elimination of quinapril and quinaprilat.
Angiotensin II could presumably serve as a specific antagonist-antidote in the setting of quinapril overdose, but angiotensin II is essentially unavailable outside of scattered research facilities. Because the hypotensive effect of quinapril is achieved through vasodilation and effective hypovolemia, it is reasonable to treat quinapril overdose by infusion of normal saline solution.
As individual monotherapy, quinapril is an effective treatment of hypertension in once-daily doses of 10 to 80 mg and hydrochlorothiazide is effective in doses of 12.5 to 50 mg. In clinical trials of quinapril/hydrochlorothiazide combination therapy using quinapril doses of 2.5 to 40 mg and hydrochlorothiazide doses of 6.25 to 25 mg, the antihypertensive effects increased with increasing dose of either component.
The side effects (see WARNINGS) of quinapril are generally rare and apparently independent of dose; those of hydrochlorothiazide are a mixture of dose-dependent phenomena (primarily hypokalemia) and dose-independent phenomena (e.g., pancreatitis), the former much more common than the latter. Therapy with any combination of quinapril and hydrochlorothiazide will be associated with both sets of dose-independent side effects, but regimens that combine low doses of hydrochlorothiazide with quinapril produce minimal effects on serum potassium. In clinical trials of ACCURETIC, the average change in serum potassium was near zero in subjects who received HCTZ 6.25 mg in the combination, and the average subject who received 10 to 40/12.5 to 25 mg experienced a milder reduction in serum potassium than that experienced by the average subject receiving the same dose of hydrochlorothiazide monotherapy.
To minimize dose-independent side effects, it is usually appropriate to begin combination therapy only after a patient has failed to achieve the desired effect with monotherapy.
Patients whose blood pressures are not adequately controlled with quinapril monotherapy may instead be given ACCURETIC 10/12.5 or 20/12.5. Further increases of either or both components could depend on clinical response. The hydrochlorothiazide dose should generally not be increased until 2 to 3 weeks have elapsed. Patients whose blood pressures are adequately controlled with 25 mg of daily hydrochlorothiazide, but who experience significant potassium loss with this regimen, may achieve blood pressure control with less electrolyte disturbance if they are switched to ACCURETIC 10/12.5 or 20/12.5.
For convenience, patients who are adequately treated with 20 mg of quinapril and 25 mg of hydrochlorothiazide and experience no significant electrolyte disturbances may instead wish to receive ACCURETIC 20/25.
Regimens of therapy with ACCURETIC need not take account of renal function as long as the patient's creatinine clearance is >30 mL/min/1.73 m2 (serum creatinine roughly ≤3 mg/dL or 265 µmol/L). In patients with more severe renal impairment, loop diuretics are preferred to thiazides. Therefore, ACCURETIC is not recommended for use in these patients.
ACCURETIC is available in tablets of three different strengths:
10/12.5 tablets: pink, scored elliptical, biconvex, film-coated tablets coded "PD 222" on one side. Each tablet contains 10 mg of quinapril and 12.5 mg of hydrochlorothiazide.
NDC 0071-3112-23: 90 tablet bottles
20/12.5 tablets: pink, scored triangular, film-coated tablets coded "PD 220" on one side. Each tablet contains 20 mg of quinapril and 12.5 mg of hydrochlorothiazide.
NDC 0071-5212-23: 90 tablet bottles
20/25 tablets: pink, round, biconvex, film-coated tablets coded "PD 223" on one side. Each tablet contains 20 mg of quinapril and 25 mg of hydrochlorothiazide.
NDC 0071-7225-23: 90 tablet bottles
Dispense in tight containers as defined in the USP.
(quinapril HCl/
20 mg/25 mg*
90 Tablets
Rx only
(quinapril and
10 mg/12.5 mg*
90 Tablets
Rx only
quinapril hydrochloride and hydrochlorothiazide tablet, film coated |
quinapril and hydrochlorothiazide tablet, film coated |
quinapril and hydrochlorothiazide tablet, film coated |
quinapril and hydrochlorothiazide tablet, film coated |
Labeler - Parke-Davis Div of Pfizer Inc (829076962) |
Establishment | |||
Name | Address | ID/FEI | Business Operations |
Pfizer Manufacturing Deutschland GmbH | 341970073 | ANALYSIS(0071-0223, 0071-3112, 0071-5212, 0071-7225) , MANUFACTURE(0071-0223, 0071-3112, 0071-5212, 0071-7225) , PACK(0071-0223, 0071-3112, 0071-5212, 0071-7225) |


text:
Apple flexed its wallet today in a way Facebook has been scared to do. Tech giants make money by the billions, not the millions, which should give them an easy way to break into premium video distribution: buy some must-see content. That's the strategy I've been advocating for Facebook but that Apple actually took to heart. Tim Cook wrote lines of zeros on some checks, and suddenly Steven Spielberg, JJ Abrams, Reese Witherspoon, Jennifer Aniston, and Oprah became the well-known faces of Apple TV+.
Facebook Watch has…MTV's The Real World? The other Olsen sister? Re-runs of Buffy The Vampire Slayer? Actually, Facebook Watch is dominated by the kind of low-quality viral video memes the social network announced it would kick out of its News Feed for wasting people's time.
And so while Apple TV+ at least has a solid base camp from which to make the uphill climb to compete with Netflix, Facebook Watch feels like it's tripping over its own feet.
Today, Apple gave a preview of its new video subscription service that will launch in fall offering unlimited access to old favorites and new exclusives for a monthly fee. Yet even without any screenshots or pricing info, Apple still got people excited by dangling its big-name content.
Spielberg is making short films out of the Amazing Stories anthology that inspired him as a child. Abrams is spinning a tale of a musician's rise called Little Voice Witherspoon and Aniston star in The Morning Show about anchoring a news program. Oprah is bringing documentaries about workplace harassment and mental health. Apple even has the Seasame Street gang teaching kids how to code.
This tentpole tactic will see Apple try to draw users into a free trial of Apple TV+ with this must-see content and then convince them to stay. And a compelling, exclusive reason to watch is exactly what's been missing from…Facebook Watch. Instead, it chose to fund a wide array of often unscripted reality and documentary shorts that never felt special or any better than what else was openly available on the Internet, let alone what you could get from a subscription. It now claims to have 75 million people Watching at least one minute per day, but it's failed to spawn a zeitgeist moment. Even as Facebook has scrambled to add syndicated TV cult favorites like Firefly or soccer matches to free, ad-supported video service, it's failed to sign on anything truly newsworthy.
That's just not going to fly anymore. Tech has evolved past the days when media products could win just based on their design, theoretical virality, or the massive audiences they're cross-promoted to. We're anything but starved for things to watch or listen to. And if you want us to frequent one more app or sign up for one more subscription, you'll need A-List talent that makes us take notice. Netflix has Stranger Things. HBO has Game Of Thrones. Amazon has the Marvelous Mrs. Maisel. Disney+ has…Marvel, Star Wars, and the princesses. And now Apple has the world's top directors and actresses.
Video has become a battle of the rich. Apple didn't pull any punches. Facebook will need to buy some new fighters if Watch is ever going to deserve a place in the ring.
Source of the article – TechCrunch


text:
Narnia is a triangular shawl worked from the top down. This shawl was quite challenging for me as I learnt some new stitches that are quite a handful to do. This shawl is all about texture. It reminds me of the wood carving in my grandparents' wardrobe, and I always imagine that wardrobe was the same wardrobe in the The Chronicles of Narnia story.
I used worsted weight yarn for this pattern to make the texture pop out. As a result, not only is this shawl beautiful to look but it is very functional.
As usual pattern includes charts and written directions. I also include a picture tutorial of how to make the crochet bind-off, and tips on how to make a larger shawl and calculate the yardage needed.
Technical Editor: Chaitanya Muralidhara
Fingering weight: 290 m (319 yards)
DK weight: 300 m (330 yards)
Worsted weight: 310 m (341 yards). The sample was made using worsted weight yarn.
Needle: Fingering weight: 3.25 mm (US 3)
DK weight: 3.50 mm (US 4)
Worsted weight: 3.75 mm (US 5)
Hook (optional):
For BO 3.5 mm (E)
For making nupp 3.0 mm (D)
Notions: Waste yarn for provisional cast-on, stitch markers.
Finished Size (aggressive blocking):
Fingering weight: 48" wide by 22" deep
DK weight: 50" wide by 23" deep
Worsted weight: 52" wide by 24" deep
Level: Advanced
All posts about this projects: click here.
How to Buy: Pattern is 11 pages in PDF includes charts and written directions. Payment by Paypal and delivery by Ravelry, no accounts required. Credit cards accepted.
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Or you can buy the e-book. Consist of 4 patterns: Bella, Metropolitan, Poison Ivy and Narnia Shawls.
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Row 12 of chart shows "p2togtbl" symbol following a ptbl. There shouldn't be a p2togtbl, it should just be a purl stitch. The written direction is correct
Row 37: there is missing cross 2 L on the chart. The written direction is correct.
Row 79: it should said lcd not special sts
a return to blogging
3 days ago


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Retractions from Springer and BioMed Central journals
London | Heidelberg, 1st November, 2016
Springer and BioMed Central are retracting 58 articles published across seven journals this week, after a thorough investigation which revealed evidence of plagiarism, peer review and authorship manipulation, suggestive of attempts to subvert the peer review and publication system to inappropriately obtain or allocate authorship.
After receiving allegations of plagiarism confined to two journals, we immediately commenced an extensive investigation across our entire portfolio. In doing so, two teams dedicated to investigating issues around research integrity, the Research Integrity Group at BioMed Central and the Springer Ethics Team, identified a group of papers across seven journals that raised concerns relating to a variety of issues.
BioMed Central has identified 28 articles that will be retracted and is investigating 40 more articles. Springer has identified 30 articles that will be retracted, with a further 9 articles that need further investigation.
We have notified the Committee on Publication Ethics (COPE), and this week we are publishing the retraction notices. Not all of the articles showed evidence of all of these issues (plagiarism, peer review and authorship manipulation) but each of them demonstrated at least one.
The decision to retract these articles is solely to correct the scientific record. We do not have any evidence to be able to determine the involvement of each of the individual authors.
Alongside investigation into the identified papers, we have taken action to ensure that no further compromised papers from this group can continue through to publication. In addition, we have revised our policies on changes to the authorship list.
As a matter of course, early this year we began an audit of BioMed Central journals to track adherence to editorial policy. This has now been updated to look for potential hallmarks of abuse, such as non-specific or shared email addresses, assess peer review quality and look for changes in manuscript titles, authorship and content.
In addition, Springer has initiated a task force to better understand current patterns in abuse cases based on these experiences, with the aim to further develop our checks and balances.
Furthermore, we will continue to raise awareness about these issues amongst our authors and editors as well as the wider research community, and we are exploring new ways to check manuscripts on submission.
The peer review process is one of the cornerstones of quality, integrity and reproducibility in research, and we take our responsibilities as its guardians seriously. It is a system which is based on trust, and we are seeing more concerted and practiced efforts by some groups to subvert it. We are vigilant in identifying when this happens and correcting the scientific record, and we are proactively working with COPE to prevent future instances like this.
The list of articles can be found here.
Amy Bourke-Waite | Head of Communications | BioMed Central | email@example.com


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High fibre diet ingredient IP6 backed for prostate cancer prevention
Writing in Cancer Prevention Research, monitored prostate cancer progression in mice fed with inositol hexaphosphate (IP6) – a major component of high-fibre diets, but also available as a dietary supplement – or a control diet .
Led by Komal Raina from the University of Colorado Cancer Center, USA, the team used MRI to monitor the progression of prostate cancer in the mice, finding that feeding with what is believed to be one of the main active ingredients of a high-fibre diet (IP6) blocked prostate tumours from making the new blood vessels they needed to supply themselves with energy.
Without this energy, prostate cancer couldn't grow, they said.
"The study's results were really rather profound," said Raina. "We saw dramatically reduced tumour volumes, primarily due to the anti-angiogenic effects of IP6."
"These findings show that oral IP6 supplement blocks growth and angiogenesis of prostate cancer in the TRAMP model in conjunction with metabolic events involved in tumour sustenance," wrote the research team.
"This results in energy deprivation within the tumour, suggesting a practical and translational potential of IP6 treatment in suppressing growth and progression of prostate cancer in humans," they explained.
Cultural differences
The US-based researchers noted that while the rate of prostate cancer is similar between Asian and Western populations, the way in which the condition progresses is significantly different between the two.
"Researchers have long been looking for genetic variations between Asian and Western peoples that could explain the difference in prostate cancer progression rates," explained Raina. "Now it seems as if the difference may not be genetic but dietary."
"Asian cultures get IP6 whereas Western cultures generally do not," he added.
Study details
Mice genetically programmed to be predisposed to prostate cancer were given either a control diet or a diet supplemented with IP6.
Beginning at four weeks of age, the mice were fed with 1%, 2%, or 4% (w/v) IP6 in drinking water or only drinking water until 28 weeks of age. The mice were monitored using MRI over the course of study.
The team found that the IP6 supplementation blocked the formation of new blood vessels in the tumour sites – meaning that the tumours could not grow and more.
Likewise, treatment with IP6 slowed the rate at which prostate cancers metabolized glucose, said the research team.
Source: Cancer Prevention Research
Published online ahead of print, doi: 10.1158/1940-6207.CAPR-12-0387
"Inositol Hexaphosphate Inhibits Tumor Growth, Vascularity, and Metabolism in TRAMP Mice: A Multiparametric Magnetic Resonance Study"
Authors: Komal Raina, Kameswaran Ravichandran, Subapriya Rajamanickam, Kendra M. Huber, Natalie J. Serkova, Rajesh Agarwal


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Beatles' First Record Contract Worth $93,750
By Britta Schmitz NEW YORK, Sept. 20 – "Welcome everybody to our live auction here today in New York City for our Beatles memorabilia. It is my pleasure to be your auctioneer", said TV art historian Elyse Luray. Heritage Auctions had a special treat for wealthy Beatles fans around the world: the Uwe Blaschke Beatles Collection from Hamburg was brought under the hammer on Saturday, Sept. 19 at the Ukrainian Institute of America. "Everything goes back to Hamburg, it's amazing," Dean Harmeyer, Consignment Director at Heritage Auctions and a Beatles expert, told Europa Newswires, referring to the two years that [Read More]


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Stainless Shell Submersible 3.2GPM 4 Deep Well Water DC Pump 24V. Volts:24V Amps:5.0MAX;Pump lift:330ft(100M). Flow Rate: 3.2 GPM (12 LPM). Inlet Screen: 50 Micron Stainless.
Existing Power Cord: 9 ft. Dimensions L x W x H in. : 3-15/16" x 3-15/16" x 12.95.
Offers a solution to your remote water needs. Designed to be used with solar panels and 24v battery systems. This means Easy Hookup to most any existing solar panels or wind generator systems. Can be used with or without components such as voltage controllers.Can be used for livestock watering, irrigation, ponds, remote homes and cabins. Unique water blocked cable connector is impervious to water leakage and condensation problems preventing water-wicking. Great for livestock watering Deep well, remote home and cabin. For 4 wells or larger.
Quick disconnect with "Watertight-Gland" Design Pat Pend. Corrosion-proof housing with stainless-steel fastener. State of the art solid diaphragm.
Pump Design: Positive Displacement 3 Chamber Diaphragm Pump. Motor: Permanent Magnet Thermally Protected. Internal Bypass: 105-110 PSI Max. Outlet Port: 1/2 (12.7mm) Barbed Fitting. Inlet: 50 Mesh Stainless Steel Screen.
Don't use any submersible pump for petrol/gasoline, petroleum products, solvents, thinners or any other fammable liquid with a flash point below 82 degree(180F). Not for use where flammable vapors are present. Thank you for your support.We are not responsible for undeliverable address. Dear friend, your happy is very important to me! We stand behind every product we sell.
You can enjoy top-quality product and high-quality services from us, Trust me that you will have a pleasant shopping experience in here. We will be happy to assist you.We would try our best to serve you with any question / problem. This item is in the category "Home & Garden\Home Improvement\Electrical Supplies\Alternative Energy Supplies\Solar Power Supplies\Solar Water Pumps & Kits".
The seller is "industrybestmen" and is located in this country: CN. This item can be shipped worldwide.


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12" w/ full color application
Our upcycled mats save useable rubber from entering a landfill. We are Earth's original neoprene upcycling company. We take everything from wetsuits, gaskets, weather-stripping, wheelchair seat molds, stock car tires, and plenty more "clean" donations to make up what we call "LAVA RUBBER". As we cut our shapes, we reprocess over two tons of material every month. Keeping this material out of landfills has been our priority since sesh one. In turn, Mother Nature cosmically hooks us up with conscious customers like yourself. All scrap donations are privately collected. All Moodmats are recycled and finished in NJ, U.S.A. We bring to you the highest quality Earth friendly mats on the planet. Enjoy! Much LOVE, Moodmats


text:
CodyCross is developed by Fanatee, Inc and it is one of the most popular games. Until now it has more than 50,000,000 installations. You find out the solutions of the crosswords while exploring different sceneries. This way you test your knowledges in different fields while completing each puzzle. Here you will find the answer for the question of Group 1312 Puzzle 2 from Street Fair pack.
Question: Chekhov's Last Play: The Cherry __
Answer: Orchard. Use this on your crossword: ORCHARD
Answer: Orchard. Use this on your crossword: ORCHARD
In case you find out any wrong answer, let us know and we will fix it as soon as possible.
Back to the pack: Street Fair Puzzle 2 Group 1312 Answers


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1975 Harley-Davidson FXE Super Glide
2-cyl. 1207cc/65hp
Protect your 1975 Harley-Davidson FXE from the unexpected.
Model overview
Model description
Harley-Davidson's Superglide of 1971 was an ingenious combination of the company's existing parts. Willie G. Davidson was the brains behind the idea, and borrowed significantly from the choppers that became fashionable on the heels of the movie "Easy Rider". After AMF bought Harley-Davidson, the company and was looking for a niche that the Japanese and European manufacturers couldn't touch.
Willie G. Davidson combined the frame from the FL Big Twin with the 74 cubic inch Shovelhead engine and gearbox, minus the electric start and large battery. The short forks and fat front end of the FL were replaced by the Sportster's lighter and longer forks, with the signature small headlight but with the dual 3.5 gallon gas tanks of the FLH. The seat and fender, meanwhile were a combination fiberglass items offered as an option on the 1970 Sportster.
Officially dubbed the FX Superglide by Harley, it quickly earned the nickname "Night Train" and combined a kicked out front end and laid back seat. Cycle World tested it at 108 mph, with a quarter mile time of 14.43 seconds and fuel economy of 47 mpg. The unpopular combination seat was dropped in 1972 for a more conventional steel fender and separate seat. In 1973, a single 3.5-gallon tank was fitted, as was a front disc brake.
Electric start was offered on the FXE in 1974 and outsold the kick start version two-to-one. The kick-start version was eventually dropped. The original Night Train featured two low pipes with one muffler, then two separate pipes were offered with a balance pipe below the air cleaner. In 1978, the FXS Low Rider was launched with the seat scooped out, shorter rear shocks, and the front forks angled out still further. The short drag bars were mounted on uprights, the paint was silver and the cases, heads and barrels finished in black crackle paint. The pipes joined in one megaphone muffler, and the seat featured a rear "sissy bar."
For 1979 the FXEF Fat Bob was introduced. It was a Low Rider fitted with dual tanks that totaled five gallons and had higher bars. The Fat Bob was available either with cast wheels or wire wheels, still 19 inches up front and 16 inches in the rear. Electronic ignition was fitted and the 80 cubic inch engine was an optional extra. The FXWG Wide Glide of 1980 was a Fat Bob with wider triple clamps and a 21-inch front wheel, trimmed front fender and ducktail rear. Foot controls moved forward to become highway pegs and the black factory finish included flames.
1980 saw the black and gold FXB Sturgis, named after the famous Harley-Davidson rally held in South Dakota. It featured extra padding on the seat, optional electric start was optional and the "B" in FXB stood for belt final drive, although the primary drive was still by chain. The 1981 FXE, FXS, FXWG and FXB models all had four speed gearboxes and electric start. Engines were rigidly mounted, but that changed in 1983 when Harley-Davidson bought itself back from the AMF conglomerate.
There is a wide array of options and small differences with these Superglides, so documented history and originality are key to determining value and desirability and more extensive research is recommended when shopping for a true collector bike. For a casual classic cruiser for weekend rides, however, the Superglide makes a great choice with affordability, reliability and comfort as some of its main virtues.


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The Dragonian's Witch
Meg Xuemei X
(The First Witch, #1)
Publication date: June 12th 2017
Genres: Adult, Paranormal, Romance
He abducts me to find his fated mate, unaware that I am she.
I am Freyja, the First Witch. I was born with a cruel curse: anyone I touch with my bare skin will die an agonizing death. That is, until a formidable, drop-dead gorgeous Dragonian prince invades my forest home.
The prince's lust burns hot and bright for me, yet he resists, wanting his destined witch more. The oracle promises the witch will be his true queen and bring him the greatest kingdom on Earth. Knowing he's the only man who can touch me, I crave his scorching caress. But I've sworn never to reveal that I am the witch. Not until he chooses me above her.
When the mating frenzy drives both of us to the brink of insanity, someone has to give, but it won't be me.
I surveyed the surroundings. If I escaped into the woods, Lucas would find me. The shifter's nose had to be as good as my wolves'. That was why Ares had brought him along. I wondered what his animal was. Judging from his size, he could be a white lion or a bear.If I escaped to the plains, the guardians would spot me. They weren't in league with me yet. If Ares caught me running away, he would chain me for the rest of the trip.
"Why are we stopping here, Ares?" the horned Dragonian asked.
"Freyja needs a bath," Ares said with irritation.
"The wolf girl?" the horned one asked. "And you let her have her way? We need to be on our way. We've wasted enough time just tracking her."
Ares snarled. "I'll decide what we need or don't need."
The others gathered around in the clearing, sitting on the rocks. Some of them took off their boots with satisfied groans.
That was exactly what I'd planned for them to do—to get in the water with me. Over four months on the road, rushing from one place to another to look for me, they had to be desperate for the feel of a warm woman. When they saw me naked, their needs would be raging. And when they came for me, they'd get what they deserved.
I would soon be reunited with my pack.
I removed my gloves, kicked off my boots, and dropped my cloak. I breathed in the fresh, damp air. The lake smelled different from the hot spring in my forest, but its earthy scent blending with the sweet honeysuckle was equally pleasant.
What would come next might not be as pleasant, but I had to gain back my freedom.
Within seconds, I was clad in only my undergarments. My skin prickled with exhilaration as it met the clean air.
Ares cleared his throat to remind me of my modesty. If he was so concerned about my decency, why wasn't he turning around as well?
His men stopped what they were doing and stared at me.
I slowly pulled the last of my garments over my head and lazily stretched my limbs. My bountiful breasts and perky, red nipples were generous for every eye to see and appreciate.
As I twisted my torso for another long stretch and bent down, I saw the men's jaws drop in shock. Yet none of them moved their heated gaze from me.
I straightened and turned away from them, my fingers on the top lines of my panties, ready to pull it off my long, toned legs.
"Freyja!" Ares shouted.
I wheeled toward him. "What?" I asked innocently.
"Turn around!" he roared at his men. "Don't fucking look at her if you want your fucking eyes stay in their sockets!"
Of course, they wanted their eyes staying in their sockets. The men obeyed, though slowly.
Wonderful! Ares—the prude—had just sabotaged my perfect plan.
But he wasn't that prudent since he himself hadn't turned around. His gaze, heated, dark, and furious, locked with mine. I tilted my head in challenge. What's the harm in having a look? You're looking.
His gaze dipped lower to my breasts, then lower—I'd pulled my panties half an inch down. When he tore his eyes from my body and stayed on my face by sheer will, a sudden fire of possessiveness leapt in them, turning his irises deeply molten gold.
"Stop what you're doing," he said, his voice hoarse as if he hadn't spoken for a while.
"Why?" I asked.
"Shouldn't you cover yourself?" He seemed incredulous at my innocent question.
"But I'm going to have a bath," I said. "Who bathes with their clothes on?"
"There are men around!" he said. "You can't go traipsing around naked in the wilderness."
"Why do you think I even consider any of them, or you," I asked, "a man? Haven't you seen a naked woman before? I'm sure your men need to wash themselves, too. Their smell, yours included, nearly choked me half to death from a mile away."
Actually he smelled really good.
I heard someone chuckle. Ares growled nastily and the chuckles died off immediately.
"It's a big lake," I said with a small shrug. "There's plenty of room for all of us."
"Like hell I'll let them share the lake with you naked," he said. "There're social rules."
"But you just said we're in the wilderness," I said, putting confusion into my voice. "Who's going to govern the rules?"
"I am," he said. Then he yelled at the men. "Go patrol the perimeter and don't look this way."
The men picked up their weapons and slowly scattered.
"Are you sending them away so you can get into the lake with me alone?" I asked.
"No, I'm not getting in the lake with you," he said. "But I'll watch you. If you think you're clever enough to pull this stunt and slip away, think twice. So far, I've been courteous. But if you keep causing trouble, you'll force my hand. Then I'll have to get rough with you and tie you up and drag you behind me. I don't care that Ventus has taken a liking to you. Just remember, his fealty is always to me."
I pulled my panties off and tossed it on top of the pile of my clothes. Dark fire leapt in his eyes and his gaze drifted down toward the valley between my thighs. He wanted me. He wanted me badly. He looked like he was ready to stalk toward me.
Did I really want him to die? My body tensed at the thought.
Ares inhaled sharply, his knuckles turning white on his sides, but he didn't move toward me.
"Earth," I said, walking toward the lake. "All this drama over a bath."
"By undressing yourself like that in front of my men," he spat, "you put yourself in danger and them in a tough spot. If any of them loses control and touches you, I would have to punish them severely."
"What about you?" I asked over my shoulder, my bare feet hitting the cool water.
"I have enough self-control," he snarled.
"Right, I've learned it the hard way," I said, intentionally dipping my gaze down at the bulge at his groin covered by his sculpted armor.
His eyes glittered with amber fire. "You're now my responsibility, Freyja," he said. "I have to guarantee that you're well treated and unharmed until the day you're allowed to go your way."
"I'm so touched," I said.
Obviously, he didn't like my tone since he was probably expecting my gratitude. His next words were full of acid. "You have no problem getting completely naked but flustered at my hard-on," he asked. "Why is that?"
"You go figure it out." I brushed him off, knowing that would irk him more.
When I sent him one last glance filled with disdain, I caught such ravenous hunger in his eyes that the heat pooled within my belly again.
Author Bio:
Meg Xuemei X is an award-winning author of steamy paranormal and sci-fi romance. She finds it dreamingly delightful to be around drop-dead gorgeous alpha males who are forever tormented by her feisty heroines, formidable alien angels, wild shifters, haughty fey, dark vampires, and cunning witches.
She's visited the universe of The Empress of Mysth, The First Witch, and Dark Chemistry. Next she'll boldly go to the badland of The Wickedest Witch. At this moment, in her southern California abode, she's packing as many forbidden weapons as she can carry. Her favorite one was a magical whip.
She is always happy to hear from readers and welcome new friends on Facebook.
Facebook: facebook.com/MegXuemeiX
Email: megxuemei AT gmail.com
She'll be giddy if you sign up to her mailing list at eepurl.com/YxOcn to hear about her new release, discounts,giveaways and fun stuff!


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§Installing Play
This page shows how to download, install and run a Play application. There's a built in tutorial that shows you around, so running this Play application will show you how Play itself works!
Play is a series of libraries available in Maven Repository, so you can use any Java build tool to build a Play project. However, much of the development experience Play is known for (routes, templates compilation and auto-reloading) is provided by SBT. In this guide we describe how to install Play with SBT.
Play requires Java 1.8. To check that you have the latest JDK, please run:
java -version
You should see something like:
java version "1.8.0_121"
Java(TM) SE Runtime Environment (build 1.8.0_121-b13)
Java HotSpot(TM) 64-Bit Server VM (build 25.121-b13, mixed mode)
If you don't have the JDK, you have to install it from Oracle's JDK Site.
§Installing Play with SBT
We provide a number of sample projects that have ./sbt
and sbt.bat
launchers for Unix and Windows environments respectively. These can be found on our download page. The launcher will automatically download dependencies without you having to install SBT ahead of time.
Or, refer to the SBT download page to install the SBT launcher on your system, which provides the sbt
Note: See sbt documentation for details about how to setup sbt. We recommend that you use the latest version of sbt.
If your proxy requires user/password for authentication, you need to add system properties when invoking sbt instead: ./sbt -Dhttp.proxyHost=myproxy -Dhttp.proxyPort=8080 -Dhttp.proxyUser=username -Dhttp.proxyPassword=mypassword -Dhttps.proxyHost=myproxy -Dhttps.proxyPort=8080 -Dhttps.proxyUser=username -Dhttps.proxyPassword=mypassword
§Running Play with SBT
SBT provides all the necessary commands to run your application. For example, you can use sbt run
to run your app. For more details on running Play from the command line, refer to the new application documentation.
You are now ready to work with Play! The next page will show you how to create projects from the command line and some more detail about creating new applications.


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