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Human growth hormone for cancer patients,sugar free diet eating plan,workout supplements info,nutritional value of 2 bananas - Videos Download
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BackgroundEndometrial carcinoma is the most common neoplasm of the female genital tract, accounting for nearly one half of all gynecologic cancers in the Western world. DiscussionIn addition to the hypothalamus, GnRH-I has also been localized to the endometrium, placenta, breast, ovary, testis and prostate [2, 21a€"23].
AcknowledgementsThis work was supported by the Canadian Institutes for Health Research and the Canadian Foundation for Women's Health to PCKL.
Competing interestsThe authors declare that they have no competing interests.Authors' contributionsDWP carried out the overall experiments to complete this study and drafted the manuscript. Dog Skin ProblemsThe sound of a dog constantly scratching or licking can be as irritating as nails on a chalkboard.
AbstractAmong patients with hormone receptor (HR)-positive breast cancer, those with residual disease after neoadjuvant chemotherapy have a higher risk of relapse and poorer survival than those with a complete response. In patients with breast cancer, neoadjuvant chemotherapy is used to reduce tumor burden and enable patients to choose breast-conserving surgery for tumor resection. Palbociclib does not re-sensitize T47DPAC cells to paclitaxel and antagonizes the effects of paclitaxel on T47DPARCell counting experiments showed that the growth inhibitory effects of concurrent combination therapy with palbociclib and paclitaxel were similar to those of single-agent palbociclib (Fig. We would like to acknowledge Nancy Azizian for technical support with the western blotting experiments and Stephanie Deming and Markeda Wade from the Department of Scientific Publications at The University of Texas MD Anderson Cancer Center for manuscript editing. Source of fundingThis work was supported in part by Komen for the Cure Catalytic Award KG090341 (AMG-A), Komen for the Cure Grant SAC 100004 (AMG-A), American Cancer Society Research Scholar Grant 121329-RSG-11-187-01-TBG (AMG-A), The Commonwealth Foundation for Cancer Research (AMG-A). Although intensive research on pathological phenomena of endometrial cancer is currently going on, but exact cause and biological aspects of this disease are not well described yet.
It is estimated that approximately 40,000 new cases of endometrial cancer are diagnosed annually in the United States and about 7,000 women die of this disease, indicating that endometrial carcinoma is thus the fourth most common malignancy and the eighth leading cause of cancer-related death in women [1]. In the endometrium and myometrium, GnRH receptor has been detected by a radioligand-binding assay and immunohistochemistry [21]. PCKL was the recipient of a Distinguished Scholar Award from the Michael Smith Foundation for Health Research.
But don't blame your pooch for these bad habits -- a skin condition is probably the culprit.
It is intended for general informational purposes only and does not address individual circumstances. Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX;2. Importantly, the response to neoadjuvant chemotherapy has prognostic implications and might be used to improve decision making during treatment1. Cells were treated with paclitaxel alone (PAC) up to 24 hours (A), concurrent combination therapy up to 24 hours (B), palbociclib (PD) alone for up to 48 hours (C) and sequential therapy (C, D). Using western blotting, the activation status of the JNK and ERK signaling pathways was evaluated in the cells before and after stimulation with 10% FBS for 10 minutes. Two-way analysis of variance (ANOVA) was used in growth curve experiments to compare the number of cells in the control versus paclitaxel-treated cells. Therefore, we used western blotting assays to determine whether long-term exposure to paclitaxel caused changes in the expression levels of ERα in T47DPAC cells (Fig. A: Cells were treated with DMSO (control), 500 nM palbociclib (PD), 2 nM paclitaxel (PAC), or concurrent combination therapy.
We demonstrated that palbociclib has a greater effect on growth and cell cycle progression than paclitaxel: palbociclib delayed cell cycle progression and antagonized the effects of paclitaxel in both parental and paclitaxel-resistant cells treated with concurrent combination and sequential therapy in the presence of palbociclib. The Characterized Cell Line Core Facility and the Flow Cytometry and Imaging Core Facility at The University of Texas MD Anderson Cancer Center are both funded by NCI Cancer Center Support Grant P30CA016672.
Ueno, Department of Breast Medical Oncology, Unit 1354, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030.
In addition to well-documented roles of gonadotropin-releasing hormone (GnRH) in hypopituitary ovarian (HPO) axis, the agonistic or antagonistic analogs (or both) of GnRH have been shown to inhibit the proliferation of a variety of human gynecologic cancers. Although intensive research on pathological phenomena of endometrial cancer is currently going on, but exact cause and biological aspects of this disease are not well elucidated yet.Gonadotropin-releasing hormone (GnRH) is the hypothalamic hormone that mediates reproductive competence [2, 3].
A GnRH-II analog, d-Arg(6)-Azagly(10)-NH2, was purchased from Peninsula Laboratories (Belmont, CA).
1(left panel), treatment with GnRH-I resulted in a significant decrease in cell proliferation compared to control. Cell proliferation was determined by 3H-thymidin incorporation assay following treatment with GnRHs. 2, treatment with GnRH-I resulted in a significant increase in integrin I?3 expression compared to control. The protein level of integrin I?3 subunit was determined and measured by immunoblot analysis. In addition, total form of FAK was measured by this method and pFAK was normalized by the expression of total FAK. Phosphorylation of FAK was determined by Western blot analysis following treatment with GnRHs. Furthermore, Engel et al., (2005) showed that the cytotoxic GnRH analogues AN-152 and AN-207 inhibit growth of xenografted HEC1A and RL-95-2 human endometrial carcinoma cell lines into nude mice [1]. It is not a substitute for professional veterinary advice, diagnosis or treatment and should not be relied on to make decisions about your pet's health. Institute for Personalized Cancer Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX. Patients with breast cancer that is hormone receptor (HR) positive and human epidermal growth factor receptor 2 (HER2) negative are less likely than patients with HR-negative disease to achieve a pathologic complete response after neoadjuvant chemotherapy, and the lack of a pathologic complete response correlates with a higher risk of relapse and poorer outcome2. The cells were maintained at 37°C in a humidified incubator in an atmosphere of 5% CO2 and periodically tested for mycoplasma contamination.
Resistance to 5 nM paclitaxel was observed after 6 months, and the cells were allowed to recover from treatment in drug-free medium for at least 1 month before experiments were performed. In the sequential therapy, cells were treated with palbociclib (PD) for 24 hours followed by addition of paclitaxel for an additional 24 hours (C), or followed by exposure to drug-free (free) medium or paclitaxel for 24 hours after PD washout (D).
Control cells were treated with vehicle (DMSO) for the same period of time as the other cells were treated with drugs.
1B) or with 500 nM palbociclib for 24 hours followed by 4 nM paclitaxel for 24 hours in the presence of or after washout of palbociclib (Fig. For cell counting experiments, the effects of treatments were compared among all groups using one-way ANOVA. The growth of T47DPAR cells was strongly inhibited by 2 nM paclitaxel, since the number of cells in the control and treated groups was significantly different, particularly after 72 hours. For each cell line, the results were compared between control and treatment using two-way ANOVA. Cell counting was performed after 6 days of treatment and presented as percentages of control. These results may be explained by the fact that paclitaxel treatment usually leads to mitotic arrest in sensitive cells. Paclitaxel is a microtubule-stabilizing agent and, therefore, relies on active cell cycle progression to induce mitotic arrest and cell death. Cell counting was performed and the results for each treatment were presented as percentages of control.
An intermittent GnRH secretion from the hypothalamus acts upon its receptor in the anterior pituitary to regulate the production and release of two gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH).
A p38 inhibitor, SB202190, was purchased from Sigma-Aldrich Ltd.AntibodiesThe polyclonal anti-integrin I?3, polyclonal anti-phospho-FAK (Ser-722), and monoclonal anti-FAK antibodies were purchased from Santa Cruz Biotechnology, Inc. In similar, treatment with GnRH-II induced a marked increase in the protein level of integrin I?3 in these cells (Fig. In the present study, GnRH-I and -II inhibit the cell growth of HEC1A human endometrial cancer cell line. PCKL conceived of the study, and participated in its design and coordination and helped to draft the manuscript. Never ignore professional veterinary advice in seeking treatment because of something you have read on the WebMD Site.
Samples were collected (arrows) for fluorescence-activated cell sorting (FACS) and western blotting (WB) at 24 hours after addition of paclitaxel in the monotherapy experiments.
For concurrent treatment, palbociclib and paclitaxel were added simultaneously to the cell culture medium, whereas for sequential therapy, the cells were exposed to palbociclib for 24 hours prior to the addition of paclitaxel in the presence of or after washout of palbociclib. The results were considered statistically significant when the p value was less than 0.05 and only differences between each treatment and the control are shown in the figures, unless otherwise indicated. On the other hand, the growth of T47DPAC cells treated with paclitaxel was indistinguishable from that of control cells.
The T47DPAC cells showed higher constitutive activation of the JNK pathway than the T47DPAR cells did, whereas activation of the ERK pathway did not seem to differ between the two cell lines (control cells; C). 3B) in both T47DPAR and T47DPAC cells, thus indicating that both cell lines were sensitive to this drug. Accordingly, previous studies have shown that pRb deficiency increases cell cycle progression and sensitivity of breast cancer cells to DNA-damaging agents15 and neoadjuvant chemotherapy16.
Although palbociclib did not reverse paclitaxel resistance, breast cancers that did not respond to neoadjuvant chemotherapy might still be sensitive to the antiproliferative effects of palbociclib in combination with adjuvant endocrine therapies. As a result, both GnRH-I and GnRH-II resulted in a significant increase in integrin beta3 expression and evoked the activation of FAK in a time-dependent manner in these cells.
3, the treatment with GnRH-I resulted in a significant increase in the phosphorylation of FAK in HEC1A cells. Allergic DermatitisDogs can have allergic reactions to grooming products, food, and environmental irritants, such as pollen or insect bites. In the concurrent combination, samples were collected at 24 hours after simultaneous addition of palbociclib and paclitaxel into the cell culture medium. The effects of each combination treatment were compared to those of control and each drug alone. This response might be explained by the fact that the two cell lines had high constitutive levels of phosphorylated pRb protein (Fig. A (right panel): Clonogenic assays after treatment with 2 nM paclitaxel for 96 hours followed by 12 days of recovery in drug-free medium. B: Cells were treated with DMSO (control), 500 nM palbociclib, 4 nM paclitaxel, or concurrent combination therapy. Therefore, our next step was to evaluate whether the release of cells from palbociclib treatment improves the efficacy of paclitaxel in the sequential therapy. In particular, the agonistic or antagonistic analogs (or both) of GnRHs have been shown to inhibit the proliferation of a variety of human ovarian cancer cell lines in a dose- and time-dependent manner through activation of extracellular-signal regulated kinase (ERK) and p38 [9, 10].
These results indicate that the effect of both GnRH-I and GnRH-II on the inhibition of cell proliferation may be involved in the expression of integrin I?3 protein in endometrial cancer cells.
6, pretreatment with SB202190 reversed GnRH-I or -II induced phosphorylation of p38, whereas no significant difference was observed in the cells treated with only SB202190 itself.
A dog with allergies may scratch relentlessly, and a peek at the skin often reveals an ugly rash.
Cells were counted using a Cellometer cell counter (Nexcelom Bioscience) for 6 consecutive days. For sequential experiments, samples were collected at 24 hours and 48 hours after palbociclib treatment and 24 hours after addition of drug-free medium or paclitaxel. Cells were harvested at 24 hours after the addition of paclitaxel as a single drug or in sequential combination with palbociclib. 2A, right panel), confirming the acquisition of paclitaxel-resistant phenotype by T47DPAC cells. 3C, control cells; C), suggesting that constitutive activation of this pathway occurs in T47DPAR cells and persists after acquisition of resistance to paclitaxel in T47DPAC. The effects of each treatment on cell cycle distribution and cell death (sub-G1) were evaluated by fluorescence-activated cell sorting (FACS) after 24 hours.
Our washout experiments showed that pretreatment of T47DPAR with palbociclib had antagonistic effects on paclitaxel-induced cell cycle arrest and cell death. The effects of each treatment on cell cycle distribution and cell death (sub-G1) were evaluated by flow cytometry. These results indicate that HEC1A cell proliferation is dose-dependently decreased by GnRH-I and -II at these concentrations. Corticosteroids can help with itchy rashes, but the most effective treatment is to identify and avoid exposure to the allergens. For cell cycle analyses, cells were fixed in 70% ethanol, stained with propidium iodide, and analyzed using a Gallios Flow Cytometer (Beckman Coulter) and FCS Express Version 4 (De Novo Software). Palbociclib-induced G1 arrest was associated with a decrease in phosphorylation and subsequent activation of the pRb protein, which resulted in downregulation of four proteins involved in cell cycle progression through S, G2 and M phases: cyclin A, cyclin B1, p-NPM and p55CDC.
Cells were treated with DMSO (control; C) or were treated with 2 nM paclitaxel for 24 hours. C: Western blotting analyses to evaluate the status of activation of cell cycle-regulatory proteins. Yeast InfectionIf your dog can't seem to stop scratching an ear or licking and chewing her toes, ask your veterinarian to check for a yeast infection. Palbociclib has been shown to reestablish cell cycle control in breast cancer cells that are resistant to tamoxifen8,9. Drug-containing medium was then removed, and the cells were allowed to recover in drug-free medium. C, D: Western blotting of activation status of JNK and ERK pathways in T47DPAR and T47DPAC cells.
Taken together, these results suggest that GnRH may be involved in the inhibition of endometrial cancer cell growth via activation of integrin beta3 and FAK as a direct effect.
An integrin heterodimer generally consists of noncovalently linked I±- and I?-subunits, each subunit having a large extracellular domain, a single membrane spanning domain and a short, noncatalytic cytoplasmic tail. The culture medium was changed every 3 days and the cells were subdivided every 7 or 8 days. A cytoskeletal remodeling was dependent on FAK, c-Src, ERK and Rac and independent from the classic phospholipase C signaling pathway [24]. After overnight serum starvation, cells were treated with DMSO (C) or 500 nM palbociclib (PD), 4 nM paclitaxel, or concurrent combination therapy for 6 hours and then stimulated with 10% FBS for 10 minutes (+) or not (-). Likewise, concurrent combination therapy and single-agent palbociclib caused similar decreases in pRb phosphorylation and in the expression of cell cycle-promoting proteins cyclin A, p-NPM, cyclin B1, and p55CDC (Fig.
This knowledge could contribute to a better understanding of the mechanisms implicated in the therapeutic action of GnRH and its biomedical application for the treatment against endometrial cancer. There are 18 I± and I? subunits that form at least 25 distinct pairs of I± and I? heterodimers with different ligand specificity [16, 17]. All treatments were performed after 4 h serum starvation and maintain serum free condition for appropriate experimental durations to remove effect of undefined endogenous hormones or cytokines. GnRH-dependent intracellular signaling events for downstream of PKC have been characterized [25]. These results led the United States Food and Drug Administration to approve palbociclib combined with letrozole as first-line treatment for metastatic disease. 3C).Since concurrent combination therapy did not improve the sensitivity of T47DPAR and T47DPAC cells to paclitaxel, we sought to determine whether brief exposure to palbociclib prior to paclitaxel treatment would increase the sensitivity to paclitaxel (Figure 4).
Second, the fact that palbociclib did not re-sensitize T47DPAC cells to paclitaxel suggests that more caution should be exercised when the use of palbociclib in combination with taxanes is considered for cases that do not respond to neoadjuvant chemotherapy. Several groups have demonstrated that GnRH receptor occupancy resulted in the activation of ERK and c-jun N-terminal protein kinase [26, 27], members of the MAPK superfamily. However, in both T47DPAR cells and T47DPAC cells, the inhibitory effects of the sequential therapy on proliferation and cell cycle progression were similar to the effects of single-agent palbociclib as demonstrated by cell growth assays (Fig. Current ongoing clinical trials are investigating the potential benefits of palbociclib in combination with paclitaxel in patients with Rb-expressing metastatic breast cancer22. In addition to controlling cell adhesion and shape, integrins also transmit signals either by physical association with several growth factor receptors or directly through recruitment of non-receptor tyrosine kinases from the focal adhesion kinase (FAK) and Src families [19]. GnRH activation of the JNK cascade is dependent on the low molecular weight GTP-binding protein, Cdc42 [26]. Preclinical studies have shown that palbociclib administered concurrently with doxorubicin or paclitaxel antagonizes chemotherapy-induced cytotoxicity12.
Although molecular events of integrins have been recently uncovered in various cell types, their role in tumorigenesis is yet to be defined. The extracts were placed on ice for 10 min, collected into a 1.5 ml tube, and centrifuged for 10 min at 19,000 G.
In addition to the ERK and JNK cascades, the MAPK superfamily includes the p38 kinase pathway [20, 27, 28] reported that GnRH can stimulate activation of the p38 kinase pathway. FolliculitisSuperficial bacterial folliculitis is an infection that causes sores, bumps, and scabs on the skin. In contrast, treatment with palbociclib prior to paclitaxel exposure has been shown to inhibit cell growth more efficiently than paclitaxel alone13.
4B) and western blotting for cell cycle-promoting proteins (Figure 5).These results suggested that palbociclib-induced G1 arrest blocks cell cycle progression toward the mitotic phase, which impairs paclitaxel activity. Thus, it is of interest to examine whether or not integrins and FAK may be involved in GnRH-induced growth inhibition in endometrial cancer cells. The supernatants were moved to new tubes, and the concentration of supernatants was determined using Bradford assay (Bio-Rad Laboratories, Mississauga, Ontario, Canada). Activation of the p38 kinase by GnRH requires PKC, suggesting that GnRH-induced p38 MAPK activation may selectively contribute to the regulation of c-fos protooncogene expression, but not c-jun or the glycoprotein hormone I±-subunit gene. Therefore, we next sought to determine whether palbociclib washout improves the efficacy of paclitaxel in the sequential therapy. In longhaired dogs, the most obvious symptoms may be a dull coat and shedding with scaly skin underneath.
Addition of drug-free medium after palbociclib treatment allowed both T47DPAR cells and T47DPAC cells to re-enter the cell cycle, as indicated by the fact that the number of surviving cells (Fig. Folliculitis often occurs in conjunction with other skin problems, such as mange, allergies, or injury.
4B) were higher after palbociclib washout than after continuous exposure to single-agent palbociclib.
It was of interest that the overexpression of integrin I?3 subunit suppressed tumor growth [31]. So far, ligand binding and clustering are known as an important step for full integrin function and the recruitment of downstream signal transduction cascade molecules [32]. Consequently, pre-exposure to palbociclib actually seemed to attenuate the inhibitory effects of paclitaxel on growth (Fig. Numerous studies have suggested that I?3 and I±VI?3 integrins are overexpressed in solid tumors, and that this overexpression plays a role in tumor growth and invasion. It was speculated that I?3 overexpression in glioma cells suppresses, rather than stimulates, glioma growth, but that this occurs exclusively in vivo and not in vitro [31].
Previous studies revealed that the growth and metastasis of transplanted tumors in mice showed lacking of specific cell adhesion receptors, integrins or selectins [20, 33, 34]. In addition, integrin I?3 or selectin null mice showed increased primary tumor growth in vivo [35]. Nevertheless, palbociclib pretreatment did not improve the growth inhibitory effects of paclitaxel (Fig.
The cells were washed three times with PBS and precipitated with 0.5 ml 10% trichloroacetic acid for 20 min at 4A°C. In some cases, it's a genetic disease that begins when a dog is young and lasts a lifetime.
The activation of these monomeric pathways has been shown to mediate important effects of GnRH in gonadotropes such as control of gonadotropin hormone subunit transcription [26]. But most dogs with seborrhea develop the scaling as a complication of another medical problem, such as allergies or hormonal abnormalities. A previous study has also shown that in many cell types, stimulation of Gi- or Gq-coupled receptors causes FAK activation [37a€"39]. FAK also has been reported to bind to the intracellular regions of I?-integrin subunits, and to play a pivotal role as a signal integrator downstream of cell-ECM interactions and other receptor and non-receptor tyrosine kinases [40].
In this study, we demonstrated that GnRH induced FAK phosphorylation in HEC1A endometrial cancer cells. The term "ring" comes from the circular patches that can form anywhere, but are often found on a dog's head, paws, ears, and forelegs. On the other hand, GnRH-II increased FAK phosphorylation after 5 min and reached maximum rate at 20 min following treatment. Puppies less than a year old are the most susceptible, and the infection can spread quickly between dogs in a kennel or to pet owners at home.
Based on these observations, it can be suggested that activation of FAK in HEC1A cells by GnRH is mediated by elevated integrin I?3 expression. Shedding and Hair Loss (Alopecia)Anyone who shares their home with dogs knows that they shed. Phosphorylation of ERK was induced by treatment with GnRH-I and -II in this study as shown in the Results.
But sometimes stress, poor nutrition, or illness can cause a dog to lose more hair than usual.
In addition, ERK phosphorylates many cytoskeletal elements and is important for the determination of cellular morphology, and can serve as anchor proteins that direct ERK to their proper locations. If abnormal or excessive shedding persists for more than a week, or you notice patches of missing fur, check with your veterinarian. In this study, we did not see any changes of cellular morphology and adhesion property in these cells (Data not shown).
Thus, we suggest that ERK might interact with nuclear substrates such as transcriptional factors rather than cytoplasmic substrates such as cytoskeletal elements.In our previous study, we demonstrated that the antiproliferative effect of GnRH-II in ovarian cancer cells may involve p38 MAPK, which led us to investigate the role of other MAPK family members [9].
Sarcoptic mange, also known as canine scabies, spreads easily among dogs and can also be transmitted to people, but the parasites don't survive on humans. The p38 MAPK is activated by the phosphorylation on tyrosine 180 and tyrosine 182 in the activation loop and modulates cell cycle for the response to environmental stress, hormones, ligands that bind to G protein-coupled receptors, and inflammatory cytokines [42].
Demodectic mange can cause bald spots, scabbing, and sores, but it is not contagious between animals or people. Furthermore, the activation of p38 MAPK was completely blocked by SB203580 (100 nM), a specific inhibitor of p38 MAPK, in this study. In addition to this, antiproliferative effect of GnRH was reversed by pretreatment of SB203580 (100 nM). Activation of p38 MAPK can also induce apoptotic cell death, but we did not detect any evidence of apoptosis in HEC1A cells following treatment with GnRH (Data not shown). You may not see the tiny insects themselves, but flea droppings or eggs are usually visible in a dog's coat.
This result was supported by previous data using HEC1A cells, indicating that GnRH analogs did not affect cell viability after treatment [43].
It can be speculated that effects of Antide, a GnRH receptor antagonist, may have some agonistic or antagonistic effect on the cell proliferation of endometrial cancer cells. Severe flea infestations can cause blood loss and anemia, and even expose your dog to other parasites, such as tapeworms.
Thus, Antide was treated with GnRH or alone for same duration abovementioned in HEC1A cells.
In this study, we failed to observe any agonistic or antagonistic effect of Antide on the proliferation of HEC1A cells (data not shown).
It was reported that Antide showed an agonistic effect on HEC1A cell proliferation only after 6-day treatment, while no significant antiproliferative effect was observed at earlier times [43]. This result indicates that Antide may have a lower affinity to GnRH receptors than GnRH analogs.
To properly remove a tick, grasp the tick with tweezers close to the dog's skin, and gently pull it straight out. Twisting or pulling too hard may cause the head to remain lodged in your dog's skin, which can lead to infection. Place the tick in a jar with some alcohol for a couple of days and dispose of it once it is dead. In addition to causing blood loss and anemia, ticks can transmit Lyme disease and other potentially serious bacterial infections. If you live in an area where ticks are common, talk to your veterinarian about tick control products. Color or Texture ChangesChanges in a dog's skin color or coat texture can be a warning sign of several common metabolic or hormone problems.
Thus, these results suggest that GnRH may have an effect on the inhibition of cell growth of endometrial cancer cells through a direct pathway.
This knowledge could contribute to a better understanding of the mechanisms implicated in the action of GnRH and its biomedical application for the treatment against endometrial cancer.
Although this study showed an inhibitory effect of GnRH on endometrial cancer cell growth, a further study is essential to reveal the ultimate cellular change and effect of GnRH on endometrial cancer cells. Acral Lick GranulomaAlso called acral lick dermatitis, this is a frustrating skin condition caused by compulsive, relentless licking of a single area -- most often on the front of the lower leg. The area is unable to heal, and the resulting pain and itching can lead the dog to keep licking the same spot. Treatment includes discouraging the dog from licking, either by using a bad-tasting topical solution or an Elizabethan collar. Skin TumorsIf you notice a hard lump on your dog's skin, point it out to your vet as soon as possible.
Hot SpotsHot spots, also called acute moist dermatitis, are small areas that appear red, irritated, and inflamed. They are most commonly found on a dog's head, hips, or chest, and often feel hot to the touch. Hot spots can result from a wide range of conditions, including infections, allergies, insect bites, or excessive licking and chewing. Immune DisordersIn rare cases, skin lesions or infections that won't heal can indicate an immune disorder in your dog. Anal Sac DiseaseAs if dog poop weren't smelly enough, dogs release a foul-smelling substance when they do their business. The substance comes from small anal sacs, which can become impacted if they don't empty properly.
A vet can manually express full anal sacs, but in severe cases, the sacs may be surgically removed.
When to See the VetAlthough most skin problems are not emergencies, it is important to get an accurate diagnosis so the condition can be treated.
See your veterinarian if your dog is scratching or licking excessively, or if you notice any changes in your pet's coat or skin, including scaling, redness, discoloration, or bald patches.
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Blessed By God
Most Relevant Verses
And God blessed (spoke good of) the seventh day, set it apart as His own, and hallowed it, because on it God rested from all His work which He had created and done.
For in six days the Lord made the heavens and the earth, the sea, and all that is in them, and rested the seventh day. That is why the Lord blessed the Sabbath day and hallowed it [set it apart for His purposes].
And God blessed them, saying, Be fruitful, multiply, and fill the waters in the seas, and let the fowl multiply in the earth.
So he came near and kissed him; and [Isaac] smelled his clothing and blessed him and said, The scent of my son is as the odor of a field which the Lord has blessed.
And the Lord answered the angel who talked with me with gracious and comforting words.
You are fairer than the children of men; graciousness is poured upon Your lips; therefore God has blessed You forever.
And God blessed them and said to them, Be fruitful, multiply, and fill the earth, and subdue it [using all its vast resources in the service of God and man]; and have dominion over the fish of the sea, the birds of the air, and over every living creature that moves upon the earth.
He created them male and female and blessed them and named them [both] Adam [Man] at the time they were created.
And God pronounced a blessing upon Noah and his sons and said to them, Be fruitful and multiply and fill the earth.
And as for Ishmael, I have heard and heeded you: behold, I will bless him and will make him fruitful and will multiply him exceedingly; He will be the father of twelve princes, and I will make him a great nation.
Now Abraham was old, well advanced in years, and the Lord had blessed Abraham in all things.
And the Lord has blessed my master mightily, and he has become great; and He has given him flocks, herds, silver, gold, menservants, maidservants, camels, and asses.
He cried, Come in, you blessed of the Lord! Why do you stand outside? For I have made the house ready and have prepared a place for the camels.
That you will do us no harm, inasmuch as we have not touched you and have done to you nothing but good and have sent you away in peace. You are now the blessed or favored of the Lord!
After the death of Abraham, God blessed his son Isaac, and Isaac dwelt at Beer-lahai-roi [A well to the Living One Who sees me].
Then Isaac sowed seed in that land and received in the same year a hundred times as much as he had planted, and the Lord favored him with blessings.
Then Jacob asked Him, Tell me, I pray You, what [in contrast] is Your name? But He said, Why is it that you ask My name? And [the Angel of God declared] a blessing on [Jacob] there.
Accept, I beg of you, my blessing and gift that I have brought to you; for God has dealt graciously with me and I have everything. And he kept urging him and he accepted it.
Of Naphtali he said: O Naphtali, satisfied with favor and full of the blessing of the Lord, possess the Sea [of Galilee] and [its warm, sunny climate like] the south.
And God [in a distinctly visible manifestation] appeared to Jacob again when he came out of Padan-aram, and declared a blessing on him.
And Jacob said to Joseph, God Almighty appeared to me at Luz [Bethel] in the land of Canaan and blessed me
The blessings of your father [on you] are greater than the blessings of my forefathers [Abraham and Isaac on me] and are as lasting as the bounties of the eternal hills; they shall be on the head of Joseph, and on the crown of the head of him who was the consecrated one and the one separated from his brethren and [the one who] is prince among them.
And the woman [in due time] bore a son and called his name Samson; and the child grew and the Lord blessed him.
And the ark of the Lord remained in the house of Obed-edom the Gittite for three months, and the Lord blessed Obed-edom and all his household.
And it was told King David, The Lord has blessed the house of Obed-edom and all that belongs to him, because of the ark of God. So David went and brought up the ark of God from the house of Obed-edom into the City of David with rejoicing;
Have You not put a hedge about him and his house and all that he has, on every side? You have conferred prosperity and happiness upon him in the work of his hands, and his possessions have increased in the land.
And Balak said to Balaam, What have you done to me? I brought you to curse my enemies, and here you have [thoroughly] blessed them instead!
You see, I have received His command to bless Israel. He has blessed, and I cannot reverse or qualify it.
And their offspring shall be known among the nations and their descendants among the peoples. All who see them [in their prosperity] will recognize and acknowledge that they are the people whom the Lord has blessed.
For He has strengthened and made hard the bars of your gates, and He has blessed your children within you.
Then the King will say to those at His right hand, Come, you blessed of My Father [you favored of God and appointed to eternal salvation], inherit (receive as your own) the kingdom prepared for you from the foundation of the world.
Blessed above women shall Jael, the wife of Heber the Kenite, be; blessed shall she be above women in the tent.
And she cried out with a loud cry, and then exclaimed, Blessed (favored of God) above all other women are you! And blessed (favored of God) is the Fruit of your womb!
For He has looked upon the low station and humiliation of His handmaiden. For behold, from now on all generations [of all ages] will call me blessed and declare me happy and to be envied!
Bible Theasaurus
From Thematic Bible
Man » Blessed by God
And God blessed them and said to them, Be fruitful, multiply, and fill the earth, and subdue it [using all its vast resources in the service of God and man]; and have dominion over the fish of the sea, the birds of the air, and over every living creature that moves upon the earth.
He created them male and female and blessed them and named them [both] Adam [Man] at the time they were created.


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Types of Connection, Normally circuits exceeding two components have two standard varieties of connections: series and parallel. A series circuit is frequently a circuit where components are attached along only one route, therefore the present flows through a single part to reach the next one. In some circuit, voltages add up to those components connected in the circuit, and currents will be exactly the same through all components. In a parallel circuit, each unit is directly connected to the power source, so each system gets the identical voltage. The current in a really parallel circuit flows across each parallel branch and re-combines once the branches meet again.
Tips to Draw Good-looking Wiring Diagrams, A good wiring diagram has to be technically correct and clear to read. Be careful of all of the info. For example, the diagram should show the best direction in the negative and positive terminals of every element. Use the proper symbols. Learn the significance in the simple circuit symbols and judge the best ones to work with. A few of the symbols have very close appearance. You have to discover a way to tell the gaps before employing them. Draw connecting cables as direct lines. Use a dot to point line intersection, or use line jumps to signify cross lines that are not connected. Label components such as resistors and capacitors using their worth. Be sure the text placement looks clean. In general it's good to place the positive (+) supply to the top, and also the negative (-) distribution at the bottom, in addition to the logical flow from left to right. Attempt and clean up the placement reducing wire crossings.


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FREE SHIPPING on orders over $75.
12 MONTHS PROMOTIONAL FINANCING AVAILABLE* on orders of $999 or more with your Lumens credit card. See Details
Quantity Available:
ZANEEN design brings high quality European lighting crafters to discriminating clients. An industry trendsetter, ZANEEN design is an award winner for innovative style and design excellence.
The Domino Flushmount is available with the following:
- Square glass shades
- Metal base
- Designed by Yohji Terazeri
- Finish: Metallic Gray
- CSA Certified
- Made In Italy
Shade Color: White and Black, White and White
- Nine 40 Watt (500 Lumens) 120 Volt G9 Double Loop Base Halogen Lamp(s) (Not Included)
Compare Brightness:
LumensThe amount of light that comes from a bulb, which has commonly been measured in watts. The more lumens, the brighter the bulb.
WattageA measurement of the power delivered to a component of an electric circuit (allowing a one-ampere current to flow through the component under the pressure of 1 volt.)
Bulb ShapeBulb shapes are denoted with a letter, which describes the shape, and a number, which indicates the size. The number indicates the diameter of the light bulb at its widest part in eighths of an inch.
BaseThe part of the bulb that connects to the fixture and its power supply. Bulb bases are denoted with the letter E, and a number which indicates the diameter of the bulb base at its widest part in millimeters.
VoltageIndicates how much voltage a bulb can accept via the fixture it's installed in.
Light Color TemperatureThe relative color from a light source, measured on the Kelvin temperature scale. Warm light is lower in color temperature (2700-3000 K) and cool, blue light is higher (5000 K).
Average Rated LifeThe average amount time that a bulb is expected to last.
CRICRI = color rendering index. This number, which can go from 0 to 100, measures the ability of a light or bulb accurately renders colors. The higher the number, the better, with most quality bulbs these days measuring at least in the 80s.
- Fixture: Width 17.75", Height 7.5", Depth 16.88"
Manufacturer IDs: view
California Residents: Prop 65 regulations
California Proposition 65
WARNING: This product can expose you to lead, which is known in the State of California to cause cancer, birth defects or other reproductive harm. For more information go to www.p65warnings.ca.gov
Proposition 65 de la Californie
AVERTISSMENT: ce produit peut vous exposer au plomb, ce qui est reconnu par l'État de Californie comme cause de cancer, d'anomalies congénitales ou d'autres domages à la reproduction. Pour plus d'informations, visitez www.p65warnings.ca.gov
Prop. 65 de California
ADVERTENCIA: Este producto puede explonerlo al plomo, lo cual es conocido en el Estado de California como causante de càncer, defectos de namimiento y ostros daños al sistem reproductivo. Para obeneter mayor información, visite www.p65warnings.ca.gov
Need help with some of our terminology? Check out Lumens' Lighting & Design Glossary.
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Find brand new 2019 Itineo 700 motorhomes at Dicksons of Perth. This range comprises of excellent four and six berth motorhomes for both couples and families, ideal for those looking for a bit more space on their next adventure. Fitted with a variety of fixed bed layouts including central island beds, bunk beds and twin beds, these A-class motorhomes all feature swivel seats for a seamless cab to lounge transition. You won't find new Itineo 700 motorhomes anywhere else in Scotland, so make sure to arrange a viewing at Dicksons of Perth or call us for more details.
JB700- Automatic 150bhp
Berths: 4
Year: 2018
Berths: 6
Year: 2019
£60,570View Details


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Using the right software makes your job much easier and helps you get the best possible results. You can easily find the right paint combinations to please your client and quickly order the paint from a nearby store. A good field service management application, such as mHelpDesk, allows all departments of your business to smoothly coordinate their efforts, eliminating wasted time and producing happy customers.
Home Painters 80262
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Climate is another factor to consider. Sunlight, wind, rain and salty weather can all wear out exterior paint. Oil-based paint is durable against wind, rain and temperature changes, but sunlight tends to degrade it. Alkyd paint chalks and sheds very thin layers when it begins to wear. Latex paint is the more durable option for very sun-drenched and relatively dry climate areas. Latex paint with high vinyl content should be avoided, however. Acrylic resin is by far the more durable binder for outdoor latex paint.
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If there is any peeling — and there usually is somewhere — it's essential to scrape off any loose paint. This doesn't just mean the parts that are already separated from the wood and ready to fall off on their own. Each spot where paint has peeled loose needs to be scraped thoroughly until you can no longer get the sharp corner of a putty knife under any of the surrounding edges of paint. Then, the bare spot needs to be sanded until the paint edges are smooth.
Consider credentials. Before you hire someone, consider his credentials. Membership in a trade or local business group, for example, isn't a guarantee of quality work, but it shows a level of commitment and reliability on his part. Also verify whether the pro has the appropriate license(s). (You'll find the licensing information in your state at the Contractor's License Reference Site. Also check with the Better Business Bureau, the attorney general's office in your state, or a local consumer-affairs agency to learn whether the contractor has a history of unresolved complaints.
Don't let chipped paint distinguish your home. Instead, be the envy of the neighborhood with the help of Santiago & Son Anthony Professional Home Painters. Our staff listens to your needs and preferences and aims to meet your design and aesthetic needs. We never take shortcuts and never leave a job until it meets your expectations. We look forward to speaking to you about your paint project, no matter how big or small. Schedule your free estimate today to see how a new coat of interior or exterior paint can instantly add life and value to your home.
To remove a bad piece of siding, you have to pull out two rows of nails: the ones in the bad board itself, and those in the board directly above. Siding is thin and splits easily, so the tricky part of this job is pulling nails without damaging surrounding boards. A cat's paw is the best tool for digging out nails if damage to the surrounding wood doesn't matter (Photo 1).
Painting contractors must also carry out administrative and marketing duties. They prepare final accounts for customers based on the original estimates and any additional work. They analyze the cost of the job compared with the estimate to calculate their profit. They market their business through activities such as setting up websites, asking customers for references or contacting property maintenance companies with details of their services.
Residential house painters on the Handy platform have used countless gallons of paint and tons of brushes over the years. With a wealth of experience under their belts, they know the best, quickest and most cost-effective ways to get the work done. From how to achieve that perfect glossy finish to ensuring no paint drips onto your crown molding, you might find yourself picking up a few tips!
Only a dummy gets involved with so-called "contractors." Hire a qualified actual worker yourself. Check out their resume/background, etc. RULE #1..NO ADVANCE DEPOSITS! Pay daily or weekly or upon satisfied completion according your standard, not workers. Contractors are merely employment agents. If that's the way you get work done, then go ahead and waste your money and wind up with the myriad of problems enumerated upon in the news clip above. RULE#2.. NO SMOKERS. They are lighting up on your money. RULE#3: No cell phones while working. Talk on their own time after work House Painting Denver CO


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The University of Southern California's Rossier School of Education Monday unveiled a new partnership with Project Tomorrow that will support the nonprofit education organization's research and help drive future innovation in K–12 schools.
Each year, Project Tomorrow's Speak Up Research Project for Digital Learning collects feedback from K–12 educators, students, parents, district administrators, principals, technology leaders, librarians and other education professionals about the role technology plays for learning both inside and outside the classroom. Since 2003, educators at more than 30,000 schools have used Speak Up's research findings, which include insights from 5 million survey participants, according to the project website. In addition, federal, state and local decision-makers use the data to inform education policy and programs.
With USC Rossier an "exclusive higher education research partner," a news release said, the institution's faculty will have access to aggregated data sets "to support research projects and advance journal articles" with Project Tomorrow and will help develop questions for Speak Up surveys.
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Grapevine-Colleyville Independent School District CTO Kyle Berger is facing new kinds of challenges he never could have foreseen before introducing an esports program into his high schools, including taking calls from college recruiters who want to know more about some of his players and hearing from parents wondering how they can get their kids on the teams. But, as he explains in this interview, the response from students has made those tiny hassles all worth the effort.
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Undergraduate study
Outstanding employability
With a degree in Chemical Engineering from Loughborough University, you can expect to have gained a diverse skill set. This will include project management, team work, leadership, business acumen and people management as well as technical expertise, setting you up for a successful career.
Our latest graduates have achieved
£30,000. Average mean salary of those in full time graduate level employment or self-employed1
95% of graduates in employment and/or further study2
1DHLE, 2017 graduates. Mean salary, FT UK & Channel Isles first degree students in professional employment
2DLHE, 2017 graduates in employment and/or further study. UK/EU & Channel Isles, FT first degree students
Due to their unique and specialist skills, engineers are the top earners in terms of starting salaries alongside graduates from medicine and dentistry (Times Good University Guide). Chartered Engineers command even higher salaries and once you have reached this status you can expect to earn a salary of over £60,000 per year.
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Recent graduate roles and destinations
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and Dranella wrote1 hour, 21 minutes ago
I'm doing the on the farm quest. I just finished my spotting. Haven't set up in mine yet except for donkey as I have one tortoise family due and Lore needs one . So will let her spot that then have farm animals. Did you want to start that one?


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The 5 stages of RR2.http://9gag.com/gag/aydn3qq
On which one are you? Is there still hope for you?
The 5 stages of RR2.http://9gag.com/gag/aydn3qq
On which one are you? Is there still hope for you?
liked it before I opened the link
lol, if you open the link you'd like it even more
Disclaimer: I am not affiliated with 9gag in any possible manner
Haha, Evelthon, Soooo true…
Guess I'm still at stage 1 of innocence…
I'm at bargaining lol
Come on, Evelthon, you started this… Please admit at what stage are you right now?
I'm at innocence, If I was an adult I would be stupid enough to charity…then straight to povery…nvm I'm a kid I wouldn't go to prostitution…I'll just steal my parents credit card…
9gaggers knew the content before opening the link
maybe when you get to prostitution you'll get gagged, people have weird fetishes… maybe gonna have to do it 9 times
Haha I'm still at Innocence. To this day I haven't spent a single cent on in-game items (I am not including purchasing games). The reason is I always like to see how many dollars an hour I am spending - like, I could spend $100 in Asphalt 8 for what would be about 16 hours of playtime. That would be paying $6.25 an hour - only $1 less than minimum wage. Do I really want to pay a GAME minimum wage? Yes I am aware that 20,000 gems is not earn-able in 16 hours. But you get the point, I hope. If you have the time to play the game for hours, do you really want to spend money on something achievable for free?
Im at charity
Haha ok Edward, I'm in between stage 2 and 3, and afraid that i will fall into stage 4 one day…
As an_ almost _free player, being in a top level alliance means that I have to be very efficient in the way I spend gems. Usually I succeed in that, but lately some tough war seasons have reduced my balance.
i'm at stage 4, denial at the moment…
when i run out of gems i will be on stage 5, poverty…
Love it Evelthon !
Sigh…I'm at Charity lol
Im at 1.5
so true
Charity. But not to support the developers, to support myself


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"Remember that time you swatted my nose when I just wanted to say hello? Now this needs to happen."
"Here come those Kibbles N Bits you love stealing so much." Edit: wow thanks guys! This is the most karma I've received since I started posting/commenting! B-)
"Yeah... You like that? Huh? You like that?...... Hmm apparently you do like that..... Almost too much."
I thought he was like "hey your tongue is more rough than mine, mind getting that itch on my ass?"
I've often wondered if we humans just misunderstand the whole "ass" thing. To us it's a source of grossness, odors and in the case of the opposite sex, occasionally a source of arousal. But I think for animals besides humans, it's a whole different thing. They seem to use it for communication, tracking, identification, and I wouldn't be surprised - given it's got warm nobbly bits exposed - a source of heat for those in need.
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Welcome to r/Funny: reddit's largest humour depository


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Kartik Aaryan, Sara Ali Khan spotted chilling together in Shimla
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Mumbai: Rumored couple Kartik Aaryan and Sara Ali Khan, who are busy in Imtiaz Ali's directorial movie 'Love Aaj Kal ...Read more
Mumbai: With an aim to make content driven films, actor-turned-producer Jackky Bhagnani has signed three directors - Nitin Kakkar of ...Read more
Mumbai: Ever since Sara Ali Khan confessed on national television that she wants to date Kartik Aaryan, the rumours of ...Read more
Mumbai: Kartik Aryan and Sara Ali Khan are currently working together in Imtiaz Ali's next film and are often spotted ...Read more
Bangkok: Actor Akshay Kumar, known for doing his own stunts, says shooting bike stunts on the streets of Bangkok for ...Read more
Mumbai: Varun Dhawan had announced his collaboration with father and director David Dhawan for 'Coolie No 1's' remake on his ...Read more
Mumbai: Only a while back Kartik Aryan used to be romantically associated with Sara Ali Khan. However, nowadays, he is ...Read more
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Mumbai: 'Luka Chuppi' actor Kartik Aryan was snapped outside his co -star Sara Ali Khan's house. Photos of Kartik, who ...Read more


text: Ranjit Koka is a Dallas based writer/director. His films have played at festivals all over the world and won many awards. Ranjit's first documentary 'CHILDREN AND AMERICA' won 12 International Awards including Best Director and Best Picture. His documentary film BABY SITA, a story of abandoning a baby after being born as a girl and not a boy was an official entry at 2018 OSCARs. He has a Masters Degree and works as an Analyst in a Bank. Along with his regular job, he has passion for films and his latest documentary film FOOTSTEPS OF GANDHI:HOME OF GOD'S CHILDREN is a story of a couple who lived, witnessed and inspired by Mahatma Gandhi and who are following his footsteps by providing home, building lives and giving hope for abandoned, orphan and physically and mentally disabled people(including children) in the holy city of Tirupati, India. This documentary is an inspiring story of Ramaswami and his wife Varalakshmi who have taken care of more than 10,000 physically and mentally disabled men, women and children. He believes that making a documentary is a social responsibility, bringing awareness on a serious and important issue, which is otherwise ignored, to push for change and call for action in our society.