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Joseph Ekidor – Making His Way in the World with Educational Support
Joseph Ekidor is no longer a child at age 19, but a young adult looking to make his way in the world as he is on the verge of completing his secondary school education.
It's a bright future made possible only through his hard work and determination, the loving home he found at the Lewa Children's Home in Eldoret, Kenya, and the generous and loyal supporters of Bread and Water for Africa® who made it possible for him not only to attend school as a child, but complete his secondary school education.
He came from a family of five siblings being raised by their parents who, only working casual jobs when they could find work, could barely scrape by putting a roof over their heads and putting food on the table for all of them – much less pay for the education they knew their children would need to succeed, reported Lewa founder and director Phyllis Keino.
"His parents were not able pay for their children's education as the little they earn is used for basic needs," explained Phyllis. "Through the Lewa Children's Home he has been provided with an education through the Bread and Water for Africa® school fee sponsorship program."
Phyllis noted that his best subjects in the classes he attends at Sambut Secondary School in Eldoret are chemistry, physics and mathematics – which is a good thing as his dream is to pursue a career in medicine, a much-needed field in the developing country.
His teachers noted in his term one academic report that in the courses where he is struggling that the see the potential in him writing, "you are capable of doing better."
As for Joseph himself, "I really appreciate the support that you have given me since I entered Form One (freshman year)," he wrote in a letter for the supporters of Bread and Water for Africa® who made it possible to attend secondary school.
Ann Tiyaa – A Success Story 12 Years in the Making
18-year-old Ann Tiyaa is a Form Four (senior) at Sambut Secondary School in Eldoret, Kenya, who has made great strides in her life.
For one thing, she has accomplished something only few children and youth are able to do in Kenya – attend 12 years of school and poised to graduate with a bright future ahead of her.
This would not have been possible for this orphaned young woman who first found a home in the loving arms of Phyllis Keino at the Lewa Children's Home, and then began her education as a young child 12 years ago and steadily progressing through each grade, without the supporters of Bread and Water for Africa® who made it possible for Phyllis to pay her school fees.
"She was born and raised in a family of four children before her mother's demise," reported Phyllis. "She was an orphan so she was raised up in the Lewa Children's Home."
Phyllis has full faith in Ann who has already demonstrated in her young life that she has the will and determination to succeed at anything she puts her mind to.
"She is working hard to achieve her dream of becoming a journalist, and her best subjects are business studies, languages and history," added Phyllis.
In her term one academic report, her teacher expressed encouragement to Ann to "put more effort" into the subjects where she has been struggling in the knowledge that "you have the potential."
As for Ann herself, she is grateful and appreciative of the supporters of Bread and Water for Africa® school fee assistance program. In a letter of appreciation she wrote this to those who made it possible for her to continue her education to its completion:
"It is my pleasure to thank my sponsors for their efforts, and good hearts.
"If not for your support, I could not have reached where I am today or even have visions and missions…or even become the person that I am today.
"I promise you that I am going to do my best and make you proud at the end of this year. Words cannot express my gratitude. Only God knows what is in my mind.
"May God bless you very abundantly."
From Abandoned Toddler to College Student, A Poultry Farm in Full Swing, and more!
What a life it has been for Emmanuel!
We at Bread and Water for Africa® began to get to know him as a 2-year-old toddler when he was brought to the Lewa Children's Home in Eldoret, Kenya, and into the loving arms of Lewa founder and executive director Phyllis Keino after being abandoned by his mother.
Even at that tender age, Phyllis, who has become known as "mother" to hundreds of orphaned and abandoned children and who all have a special place in her heart could tell there was something exceptional about Emmanuel.
15 years ago, Emmanuel arrived at Lewa with his older brother and sister, and it didn't take long for them to become a part of the Lewa family, and for Phyllis to become the only mother he has ever known.
While most children in Kenya, and throughout the African continent for that matter, want nothing more than to be able to go to school in the knowledge that getting an education is their only chance out of a life of dire poverty, for Emmanuel, it was not just attending school – but excelling the classroom – that was his passion.
Emmanuel attended Kip Keino Primary School from Nursery to Jr. High, and in 2015, as an eighth grader, Emmanuel tackled his biggest challenge yet by scoring among the best and brightest throughout the entire country in the Kenya Certificate of Secondary Education (KCSE) examinations (similar to the SAT for high school students in the United States).
It is especially tragic for those who have the ability and determination but lack the money for school supplies and uniforms and have no choice but to take menial low-wage jobs to help support their families and themselves.
While of course we cannot say what was going through Emmanuel's mind as he filled out his application for Kapsabet High School, we must assume it was with hopeful optimism. Kapsabet is one of the most prestigious high schools in the country whose alumni include Daniel Arap Moi, the second president of Kenya.
The odds against him being accepted to Kapsabet – (where only 300 new students are accepted each year – out of an application pool of 60,000!) – were long, but as his acceptance to the class of 2019 illustrates, not insurmountable.
For Emmanuel, beating those seemingly overwhelming odds was not a matter of luck, but a testament to his ability, and his steady belief that he can do whatever he sets his mind to.
Four years later, we have just received word from Phyllis that Emmanuel is headed to Taita Taveta University in Mariwenyi, Kenya – on a full scholarship!
Taita Taveta University, a non-profit public higher education institution accredited by the Commission for University Education of Kenya, is described as "A Premier Institution in Education, Training, Research, Innovation And Community Outreach."
Beginning in August, Emmanuel will begin his studies, majoring in agribusiness; a vital field on the African continent as noted by a recent report by the World Bank on "Agribusiness Indicators: Kenya" which states:
"The importance of agriculture in the economies of sub-Saharan African countries cannot be overemphasized.
"With agriculture accounting for about 65 percent of the region's employment and 75 percent of its domestic trade, significant progress in reducing hunger and poverty across the region depends on the development and transformation of the agricultural sector.
"Transforming agriculture from largely a subsistence enterprise to a profitable commercial venture is the prerequisite and driving force for accelerated development and sustainable economic growth in Sub-Saharan Africa."
We have no doubt that one day in the not-too-distant future, Emmanuel – the same 2-year-old helpless child abandoned by his mother – will be leading the way as a driving force in helping to reduce hunger and poverty, perhaps even at the Baraka Farm right next to the Lewa Children's Home where he grew up.
Despite all Emmanuel has accomplished, we know he will never forget those who helped him attain the success he has achieved today – namely Phyllis, and the supporters of Bread and Water for Africa®. Without them, he would not have had a home, much less an education.
Upon his acceptance to Kapsabet in 2015, he expressed his sincere gratitude in a letter to the supporters of Bread and Water for Africa® writing:
"I write this letter to really appreciate for sponsoring me – for if it wouldn't have been for you, I wouldn't be where I am.
"This comes from the bottom of my heart. I promise to work hard at school and post good results as hard work pays.
"Moreover, I promise to not let you down."
The town of Mariwenyi is 400 miles, a 12-hour bus ride on the rutted Kenyan roads, from Lewa where he grew up, but a world away from how his life began and how we are certain it will evolve.
Wilson, Samuel and Joseph: Three Abandoned Brothers Find Love in Phyllis' Arms
For one brief, heartbreaking period in their young lives all that the three brothers Wilson, Samuel and Joseph had was themselves after unbelievably being abandoned by their mother.
And it was on a dark, rainy evening in Kenya when a neighbor heard their desperate crying that a concerned, compassionate neighbor came to their rescue.
Though she tried to locate the boys' mother, she was nowhere to be found – and with nowhere else to turn, the woman brought Wilson, Samuel and Joseph into the loving, welcoming arms of Phyllis Keino, the founder and director of the Lewa Children's Home, a longtime partner of Bread and Water for Africa®.
"On arrival, they were weak, hungry and very malnourished," Phyllis told us. "They came with many ailments."
In addition, never having been to school, they could neither read nor write and showed signs of being mentally challenged.
Phyllis does not select the orphaned and abandoned children who are brought to her. Whether this is by government officials, the police because their parent(s) are in prison, or caring citizens, she instantly gives them her love as if each is one of her own, because from that moment on they are.
The horrors of their past lives are thankfully unknown, but what is known is that these three boys have a present filled with a love they have likely never known, the basic necessities of life including health care and an education, and hope for a long life and a bright future – thanks to Phyllis and the supporters of Bread and Water for Africa®.

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"We had talks with 49 promising potential franchisees and multi-unit candidates on site. More than ever. More than at any other show. It is now one week after the Expo and we have already started our multi-stage partner selection process with 10 of those candidates."
Matthias H. Lehner, CEO and founder, Bodystreet, Vice President of the German Franchise Association
"VeloCulTour will definitely be on board again next year. Our entry into the franchise world was more than successful and we were able to establish new, valuable contacts at the show – especially on Thursday and Saturday. The expert panel was extremely fascinating for us too and we are already looking forward to using what we have learned this year to take a step forward next year. The organization and implementation of the Expo was very impressive and another reason, why we booked our booth for next
year right away on the last day of the show."
Kai Nüchter, Marketing Director, VeloCulTour
"After we had three very successful days at the Franchise Expo 2018, we knew right away that we would be back in 2019. Great conversations, great
contacts, and overall just great people – for a growing system like Dogstyler© this Expo definitely is the perfect platform for effective expansion management."
Holger Michels, Commercial Director, Dogstyler©
"The franchise systems on-site took the first successful steps towards a global exhibition and are now busy, to spark the second steps. The Franchise Expo is the place where the future sustainability is the focus of discussions and presentations and we will contribute to that vision again in 2019."
Thomas Anslinger, Franchise Director, TeeGschwendner
November 5 - 7, 2030
Exhibition Center, Hall 9.0


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Ionia Duvet Set Indigo indigo comforter set
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Growing Deeper
Senior Women growing deeper in their love for God and His WordThe desire of this delightful group of women is to be formed by God's truth and grow in His Word together. While most have children that are grown with families of their own, they encourage woman of all ages and stages of life to join them in this opportunity to grow in their relationship with Christ together. Come glean from the wisdom these woman share as they search out truths and applications of scripture. When: The second Thursday of each month Time: 9:30 – 11:30 Location: Women's Ministry Center, Room 224 Leader: Lauren Kinnari, 541-730-5986, email@example.com Childcare: Not Available
RegistrationThis Bible study is offered free to our Senior Ladies. Register Now For Bible Study!
September 12th – May 14th
Psalms: Discovering Authentic WorshipAuthor: Sue Edwards
This study in the book of Psalms will deepen your worship of our Almighty God. Worship includes many things – singing, praying, and serving. It is responding to God because He along is worthy of our praise. We celebrate God's character, works, and plans through worship. We declare His majesty and our acknowledgement of how great He is. Our hearts are engaged and our senses are focused on Him and Him alone. Gain a more personal understanding of what true worship looks like in our daily lives.


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A One Kids
A-One Brands, A-One Prices, A-One Service
This store was created due to the demand by our customers at A-One Clothing who asked for similar brand name quality products that they were purchasing for themselves to be available for their kids. A-One Kids sells brand new footwear and quality outdoor clothing as well as outerwear for your young, outdoor, hard playing kids.
Now you can shop for the whole family at A-One Clothing and A-One Kids. Our professionally trained staff are able to fit your kids' feet properly and ensure they are sized in the most comfortable footwear possible.


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$ 920.00 $ 1,086.00 You Save 15% ($ 166.00)
This sleek desk made of 100% solid moso bamboo offers premium quality and a great mid-century modern look. Its clean lines and small footprint make this the perfect option for those who want high quality but are short on space. Tucked underneath the generous work surface is a slim center pencil drawer, shipped with two interchangeable drawer faces - bright white or matching the rest of the desk in carmelized bamboo finish.
Its dimensions are 47" W X 23.5" D X 29.5" H.
Greenington products typically ship with LTL (heavy freight) carriers, though some smaller items ship with FedEx. Inside delivery on LTL shipments is included whenever possible (but carriers will not bring boxes into a specific room or office - inside delivery only means the carrier will lift boxes out of the truck and get them to the first dry spot, whether a garage or a landing area). Processing times with Greenington are 1-3 business days, after which items ship from Washington state. Transit times range from 1-6 days, depending on where the products are shipping to.


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Glutamates as aggrecanase inhibitors
FIELD: chemistry.
SUBSTANCE: compound is a matrix metalloproteinase or aggrecanase. The invention also relates to a pharmaceutical composition based on said compounds and a method of treating osteoarthritis, (I), where W is -C(O)-; R1 is bisphenyl, possibly containing one or more substitutes R5 and R6; and if R1 contains one or more substitutes R5 and R6, the substitutes can be identical or different; R2 is hydrogen; R3 is -CO2H, -CONHOH, -CONHR7 or -COOR7; R4 is -CONR9R10; m equals 0. The values of substitutes R5-R7, R9, R10 are as described in the claim.
EFFECT: compounds have the capacity to modulate metalloproteinase activity.
18 cl, 40 ex, 18 dwg, 6 tbl
The text descriptions are given in facsimile form.
1. The compound of formula (I)
or its pharmaceutically acceptable salt, where
W represents-C(O)-;
R1represents a biphenyl, possibly containing one or more substituents R5or R6; and if R1contains more than one substituent R5or R6the substituents may be identical or different;
R2represents hydrogen;
R3represents-CO2H, -CONHOH, -CONHR7or-COOR7;
R4is a-CONR9R10;
R5is a (C6-C10)aryl, -NHCO-(C6-C10)aryl, -NHCO-heteroaryl where heteroaryl represents a 5-membered aromatic heterocyclic ring containing one heteroatom selected from oxygen, (C1-C6)alkyl, -O-(C1-C6)alkyl or-N-(C1-C6)alkyl, where each alkyl, aryl or heteroaryl may contain one or more substituents R6and if R5contains more than one substituent R6the substituents may be identical or different;
R6represents hydrogen, halogen, -OH, -CO2R7, (C2-C6)quinil, (C2-C6)alkenyl, -O-(C1-C )alkyl-(C3-C6)cycloalkyl, -O-(C1-C6)alkenyl, -O-(C1-C6)aryl, O-heteroaryl where heteroaryl represents a 5-membered saturated heterocyclic ring containing 2 heteroatoms selected from oxygen, and the specified ring condensed with a 6-membered aromatic ring, -O-(C1-C6)alkyl, containing as substituent (C6-C10)aryl, each aryl may contain one or more substituents R13;
R7represents hydrogen or (C1-C6)alkyl;
R9represents hydrogen or (C1-C6)alkyl may contain one or more substituents R12;
R10is a (C1-C6)alkyl may contain one or more substituents R12;
R12is a (C6-C10)aryl may contain one or more substituents R13A 5-membered saturated heterocyclic ring containing 2 heteroatoms selected from oxygen, where the specified ring condensed with a 6-membered aromatic ring;
R13represents a halogen, -O-(C1-C6)alkyl, -CO2H, -OH, -CF3hydrogen, (C1-C6)alkyl, (C6-C10)aryl, 5-6-membered heteroaryl containing 1 heteroatom selected from nitrogen and sulfur, (C2-C6 )alkenyl, (C2-C6)quinil, (C3-C6)cycloalkyl containing as Deputy-HE; (C6-C10)aryl containing as Deputy-NH2or (C6-C10)aryl containing as a substituent-O-(C1-C6)alkyl;
m is 0;
n is 0-4; and
p is 2.
2. The compound or pharmaceutically acceptable salt of the compound according to claim 1, wherein R3represents-CO2N.
3. The compound or pharmaceutically acceptable salt of the compound according to claim 1, characterized in that the compound or pharmaceutically acceptable salt of the compound is an S-enantiomer relative to the carbon atom to which the group R4.
4. The compound according to claim 1 of formula (Ia)
or its pharmaceutically acceptable salt, where
R1, R2and R4defined in claim 1.
5. The compound according to claim 4 or pharmaceutically acceptable salt, characterized in that
R4represents a
6. The compound according to claim 4 or pharmaceutically acceptable salt, characterized in that
R4represents a
7. The compound according to claim 4 or pharmaceutically acceptable salt, characterized in that
R4represents a
8. Joint who according to claim 1, wherein R13represents a halogen.
9. The compound according to claim 1, wherein R5represents -(C1-C6)alkyl.
10. The compound according to claim 1, wherein R6represents hydrogen.
11. The connection of claim 10, wherein R7represents hydrogen.
12. The compound according to claim 1, characterized in that
R4is a-CONR9R10;
R5represents -(C1-C6)alkyl;
R6represents hydrogen;
R7represents hydrogen;
R12is a (C6-C10)aryl;
R9represents hydrogen and
R10is a (C1-C6)alkyl, possibly substituted by one or more of R12.
13. The compound or its pharmaceutically acceptable salt according to claim 1, where the compound is selected from the following:
N1-benzyl-N2-[(4'-ethyl-1,1'-biphenyl-4-yl)carbonyl]-L-α-gluten is h,
N2-(1,1'-biphenyl-4-ylcarbonyl)-N5-hydroxy-N1-[2-(3-methoxyphenyl)ethyl]-L-glutamate is,
N2-[(2,2'-dimethyl-1,1'-biphenyl-4-yl)carbonyl]-N1-(3-methoxybenzyl)-L-α-gluta is in,
N2-(1,1'-beef the Nile-4-ylcarbonyl)-N 1-(4-phenylbutyl)-L-α-glutamine,
N2-(biphenyl-4-ylcarbonyl)-N1 N2-(biphenyl-4-ylcarbonyl)-N1-(1-methyl-1-phenylethyl)-L-α-glutamine,
tert-butyl N2-(biphenyl-4-ylcarbonyl)-N1-(1-phenylethyl)-L-α-glutamine,
4'-{[((1S)-3-carboxy-1-{[(3,4,5-trimethoxybenzyl)amino]carbonyl}propyl)amino]carbonyl}biphenyl-3-carboxylic acid,
N2-[(3',4'-dimethoxybiphenyl-4-yl)carbonyl]-N-(3,4,5-Tr is methoxybenzyl)-L-α-glutamine,
N-[2-(4-forfinal)-1,1-dimethylethyl]-N2-[(3'-methylbiphenyl-4-yl)carbon is l]-L-α-glutamine,
N-(1,1-dimethyl-2-phenylethyl)-N2-[(4 hydroxybiphenyl-4-yl)carbonyl]-L-α-glutamine,
N2-{[4'-(methyl bromide)biphenyl-4-yl]carbonyl}-N-(3,4,5-trimethoxybenzyl)-L-α-glutamine,
N2-{[3'-(methyl bromide)biphenyl-4-yl]carbonyl}-N-(3-methylbenzyl)-L-α-glutamine,
N2-[(4'-chlorobiphenyl-4-yl)carbonyl]-N-[2-(4-FPO is phenyl)-1,1-dimethylethyl]-L-α-glutamine,
N2-({3'-[(3,5-dimethoxyphenoxy)methyl]biphenyl-4-yl}ka is bonyl)-N-(3-methylbenzyl)-L-α-glutamine,
N-benzyl-N2-{[4'-(biphenyl-2-ylethoxy)biphenyl-4-yl]carbonyl}-L-α-glutamine and
14. The compound or pharmaceutically acceptable salt of the compound according to item 13, where the compound is selected from the following:
N2-[(3',5'-diferuloyl-4-yl)carbonyl]-N-(1,1-dimethyl-2-phenylethyl)-L-α-gluten is h,
15. The composition for modulating the activity of metalloproteinases, which is a matrix metalloproteinase or aggrecanases containing an effective amount of a compound or pharmaceutically acceptable salt of the compound according to claim 1, and a pharmaceutically acceptable carrier.
16. The composition according to item 15, wherein the compound or pharmaceutically acceptable salt of the compounds selected from the following:
N2-[(3',5'-diferuloyl-4-yl)carbon is l]-N-(1,1-dimethyl-2-phenylethyl)-L-α-glutamine,
17. The composition according to item 15, wherein the pharmaceutically acceptable carrier is suitable for oral administration, the composition is presented in a dosage form for oral administration.
18. A method of treatment of osteoarthritis, including the introduction of an effective dose of a compound according to claims 1 to 14 or its pharmaceutically acceptable salt.
FIELD: chemistry.
SUBSTANCE: pharmaceutical compositions containing at least one compound of formula (IIIa) or (IIIb) or (IVa) or (IVb), where -X- and Y are described in the claims, or pharmaceutically acceptable salts, esters or amides thereof and a pharmaceutically acceptable carrier, which can be used in processes with modulation or E- and P-selectin expression.
EFFECT: obtaining low-molecular non-glycoside and non-peptide compounds, capable of creating antagonism to selectin-mediated processes.
11 cl, 38 ex, 3 tbl
FIELD: medicine, pharmaceutics.
SUBSTANCE: claimed invention relates to chemical-pharmaceutical industry. Pharmaceutical compositions including, at least, one compound of formula where -X- represents, for instance, group of formula and Y represents, for instance, group of formula or its pharmaceutically acceptable salts, esters or amides, or pro-drugs and pharmaceutically acceptable carrier, which is acceptable in therapy, can be applied for modulation in vitro and in vivo processes of binding, mediated by binding of E-, P- or L- selectin.
EFFECT: obtaining novel floroglucin derivatives.
9 cl, 10 ex, 3 tbl
FIELD: medicine, pharmaceutics.
SUBSTANCE: present invention refers to compounds of formula Ia and their pharmaceutically acceptable salts, hydrates, solvates, esters and amides. In formula Ia , A is specified from -C(O)OR5 where R5 represents hydrogen; W represents C1-3alkylene; Y is specified from phenyl and 5-6-member heteroaryl containing one heteroatom specified from N, S, O; where any phenyl or heteroaryl Y can be optionally substituted with 1 to 3 radicals specified from halogen, C1-6alkyl, C1-6alkoxygroup, halogen-substituted C1-6alkyl and halogen-substituted C1-6alkoxygroup; Z is specified from: where left and right asterisks Z specify an attachment point between -C(R3)(R4)- and A of formula la; R6 is specified from hydrogen and C1-6alkyl; or R6 can be attached to carbon atom in Y to form a 5-7-member ring; R1 is specified from phenyl and 5-member heteroaryl containing one heteroatom specified from S, O; where any phenyl or heteroaryl R1 is substituted with a radical specified from phenylC0-4alkyl, heteroarylC0-4alkyl where heteroaryl represents 5-6-member heteroary containing one heteroatom specified from N, S, O, C3-8cycloalkylC0-4alkyl, C3-8heterocycloalkylC0-4alkyl which contains nitrogen atom as heteroatom, or C1-6alkyl; where any phenyl, heteroaryl, cycloalkyl or heterocycloalkyl group R1 can be optionally substituted with 1 to 3 radicals specified from halogen, C1-6alkyl, C1-6alkoxygroup, halogen-substituted C1-6alkyl group and halogen-substituted C1-6alkoxygroup; R2 represents C1-6alkyl group; R3 and R4 represent hydrogen.
EFFECT: preparation of the pharmaceutical composition exhibiting EDG/S1P receptor modulating properties, containing therapeutically effective amount of the compound under the invention, development of a method of treating the disease mediated by EDG/S1P receptor activity, application of the compounds for preparing a drug for prevention or treatment of the disease mediated by EDG/S1P receptor activity.
16 cl, 1 tbl, 86 ex
FIELD: chemistry.
SUBSTANCE: invention relates to novel compounds of general formula (I): , optical isomers of said compounds, as well as salts thereof having peroxisome proliferator-activated receptor subtype y (PPARy) modulating property. Values of R1, R2, X, Ar1 and Ar2 are given in the formula of invention.
EFFECT: preparation of compositions based on said compounds, as well as use of said compounds in cosmetic and pharmaceutical industry.
11 cl, 30 ex
FIELD: medicine.
SUBSTANCE: invention relates to amidines of formula (I) and to their derivatives, methods for making thereof and pharmaceutical compositions containing amidines of formula (I). According to said invention, amidines are applicable for inhibition of IL-8 induced chemotactic factor, and can be applied to produce medicine agents for treating psoriasis, ulcerative colitis, melanoma, chronic obstructive pulmonary disease (COPD), bullous pemphigoid, rheumatoid arthritis, idiopathic fibrosis, glomerulonephritis and for preventing and treating injuries caused by ischemia and reperfusion.
EFFECT: higher clinical effectiveness.
7 cl, 6 ex, 1 tbl
FIELD: chemistry.
SUBSTANCE: invention relates to novel compounds of formula (I), including its pharmaceutically acceptable salts, solvates, ethers and amides, possessing ability to bind ERα- and ERβ-estrogen receptors, to pharmaceutical composition based on them, to versions of applying claimed compounds in medication preparation and to method of binding ERα- and ERβ-estrogen receptors. (I), where R1 represents H, OH or C1-12alkoxy, or halogen; R2 represents H, OH or halogen; R3 represents C1-12alkyl, halogeno-C1-12alkyl, C3-10cycloalkyl, C1-12alkoxy or C1-12alkoxyC1-12alkyl; R4 represents H or C1-12alkoxy; R5 represents H, halogen or halogeno-C1-12alkyl; R6 represents -(Y)z-R7; R8 represents phenyl or 5- or 6-member heteroaryl, containing N, O or S as heteroatom, where said phenyl and heteroaryl are possibly substituted with OH, halogeno, halogenoC1-12alkyl or C1-12alkoxy. Values R7, Y and z are presented in invention formula.
EFFECT: novel compounds possess useful biological properties.
19 cl, 7 dwg, 1 tbl, 70 ex
FIELD: chemistry.
SUBSTANCE: in acidified indanylamines of general formula (I) R1-R4 have values given in description, A represents CH2, CHOH, B represents CH2 and R5 represents aryl or heteroaryl group, possibly substituted with substituents, listed in description. Said compounds are useful in regulation of endothelial nitrogen oxide synthase (eNOS) and, therefore they can be useful for production of medications for treatment of stable and unstable angina pectoris, Prinzmetal's angina, acute coronary syndrome, impaired heart function, cardiac infarction, stroke, thrombosis, peripheral artery occlusive disease, endothelial dysfunction, atherosclerosis, hypertension, lung hypertension, symptomatic hypertension, renovascular hypertension, erectile dysfunction, diabetes or diabetes complications, nephropathy, retinopathy, limited memory function, limited learning ability.
EFFECT: increase of composition efficiency.
37 cl, 441 ex, 2 tbl
FIELD: organic chemistry, chemical technology, medicine.
SUBSTANCE: invention relates to a new method for synthesis of derivative of thieno[3,2-c]pyridine of the formula (1): (ticlopidine and clopidogrel). Method involves interaction of compound of the formula (2e): with compound of the formula (3): or its salt wherein R represents hydrogen atom or methoxycarbonyl; each among X' and Y' represents independently chlorine, bromine atom, methanesulfonyl or p-toluenesulfonyl, and to novel intermediate compounds and methods for their synthesis. Ticlopidine and clopidogrel possess the high inhibitory activity with respect to blood platelets aggregation and antithrombosis activity.
EFFECT: simplified process of synthesis, valuable medicinal properties of compounds.
15 cl, 32 ex
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to novel ester compounds represented by the formula (1): wherein values for R1, R2, A, X, R3, R4, Alk1, Alk2, l, m, D, R8 and R9 are determined in the invention claim. Also, invention relates to inhibitor of matrix metalloproteinase (MTP), a pharmaceutical composition able to inhibit activity of MTP selectively, agents used in treatment or prophylaxis of hyperlipidemia, arteriosclerosis, coronary artery diseases, obesity, diabetes mellitus or hypertension wherein the pharmaceutical composition is prepared in capsulated formulation, and to a biphenyl compound of the formula (100) given in the invention description.
EFFECT: valuable medicinal properties of compounds.
53 cl, 78 tbl, 17 ex
FIELD: organic chemistry, pharmacy.
SUBSTANCE: invention relates to new biphenylsulfonylcyanamides of the formula (I): wherein R1 means: 1. (C1-C8)-alkyl; 4. -CnH2n-nn-Y wherein nn = 0 or 2 and n = 0-4, and n is not 0 or 1 if nn = 2; 5. CnH2n-nn-Y wherein nn = 0 or 2 and n = 1-4, and n is not 1 if nn = 2, and 1 hydrogen atom in bivalent residue CnH2n-nn is substituted with amino-group or NR(22)R(23); R2 means: 2. (C1-C)-alkyl; 4. (C2-C12)-alkenyl; 5. (C2-C8)-alkynyl; 6. -CnH2n-nn-Z wherein nn = 0 or 2; n = 0-4, and n is not or 1 if nn = 2; 7. -CnH2n-nn-Z wherein nn = 0 or 2; n = 1-4, and n is not 1 if nn = 2, and 1 hydrogen atom in bivalent residue CnH2n-nn is substituted with a residue taken among a series: 1. phenyl; 3. NR(22)R(23); 5. COOR(16); R3 and R4 mean hydrogen atom; R5, R6 and R7 mean independently of one another hydrogen atom (H), (C1-C8)-alkyl; SO2-(C1-C4)-alkyl, F, Cl, Br, J, OR(10) wherein R(10) means hydrogen atom, (C1-C4)-alkyl that is substituted if necessary with methoxy- or ethoxy-group; R(9) means OR(13) wherein R(13) means hydrogen atom, H,(C1-C8)-alkyl;X means carbonyl group, -CO-CO- or sulfonyl group; Y and Z mean independently of one another: 1. phenyl, 1-naphthyl, 2-naphthyl; 2. one of residues determined in cl. 1 substituted with 1-5 similar or different residues taken among a series: phenyl, F, Cl, Br, J, CF3, SOqR(18), OR(16), NR(19)R(20), -CN, NO2, COR(9), or two residues form methylenedioxy-group; 3. furyl, thienyl, pyridyl, benzimidazolyl, indolyl, benzothiophenyl, dihydroquinazolinyl; 5. (C3-C10)-cycloalkyl wherein cyclopropyl, cyclopentyl, cyclohexyl and indalyl are preferable; 6. one of residues determined in cl. 5 substituted with phenyl; R(16) means: 1. hydrogen atom; 2. (C1-C4)-alkyl; 3. (C1-C4)-alkyl substituted with (C1-C4)-alkoxy-group; R(19) and R(20) mean independently: hydrogen atom (H), (C1-C4)-alkyl; R(22) and R(23) mean independently of one another hydrogen atom (H) or CO-OR(24) wherein R924) means -CnH2n-phenyl wherein n = 1-4; q = 2; and their physiologically acceptable salts. Compound of the formula (I) inhibit sodium-dependent chloride-bicarbonate exchange "NCBE".
EFFECT: improved preparing method, valuable medicinal properties of compounds.
4 cl, 2 tbl, 568 ex
FIELD: chemistry.
SUBSTANCE: invention relates to compounds selected from a group comprising piperazine compounds of formula I: , where X is -CH2- or a bond; n equals 1; R1 is alkyl; cycloakyl; hydroxyethyl; benzo[1,3]dioxolyl; phenyl, which can be mono-substituted with a halide, alkyl, alkoxy, -CF3 or alkylcarbonyl; or phenyl which is di- or tri-substituted with substitutes independently selected from alkyl and halide; pyridyl which can be mono-substituted with a halide, alkyl or -CF3; furanyl which can be mono-substituted with methyl, hydroxymethyl or bromine, or furanyl which is disubstituted with an alkyl; thienyl which can be mono-substituted with methyl or chromium; pyrimidinyl; isoquinolinyl; benzhydryl; imidazolyl optionally mono-substituted with an alkyl; or thiazolyl; or X is -C(=O)- and R1 is hydrogen; R2 is indolyl, imidazolyl optionally mono-substituted with alkyl; phenyl which can be mono-substituted with a halide, alkyl, hydroxy or cyano, or phenyl which is disubstituted with a halide; pyridyl; benzothienyl; thiazolyl or thienyl; R3 is indolyl, pyridyl which can be mono-substituted with alkoxy, alkoxyalkoxy, NR31R32, morpholine, piperadine, oxopiperidinyl, oxopyrrolidinyl, pyridyl or phenyl; or phenyl which is mono-substituted with phenyl, pyridyl, alkyl, alkoxy, dialkylamino, morpholine, N-benzyl-N-alkylamino, (dialkylamino)alkoxy, phenylalkoxy or tetrahydroisoquinolinyl; or R3 denotes the group: , where Z is phenyl or pyridyl; R31 is 2-C1-C5alkoxyethyl, phenyl, pyridyl, phenylalkyl, hydroxyalkylcarbonyl, alkylcarbonyl, cycloalkylcarbonyl or phenylcarbonyl; R32 is hydrogen or methyl; R35 is alkyl, alkylcarbonyl, phenyl, pyridyl or pyrimidinyl; and R4 is phenyl-CH=CH-, where the phenyl can be mono-, di- or tri-substituted with substitutes independently selected from halide, alkyl, alkoxy and -CF3; or phenyl-CH2-CH2, where the phenyl is disubstituted with -CF3; and to optically pure enantiomers thereof, mixtures of enantiomers, such as, for example, racemates, optically pure diastereomers, mixtures of diastereomers, diastereomeric racemates, mixtures of diastereomeric racemates and mesoforms, such as salts of such compounds. The invention also relates to a pharmaceutical composition, as well as to use of compounds in any of claims 1-4.
EFFECT: obtaining novel biologically active compounds with antimalarial activity.
8 cl, 138 ex, 1 tbl
FIELD: chemistry.
SUBSTANCE: invention describes a novel compound of general formula (1), where radicals R1, R2, X1, Y and A are as described in claim 1 of the invention. The invention also describes a method of obtaining compounds of formula (1), as well as a pharmaceutical composition based on said compounds, for treating fibrosis.
EFFECT: novel compounds with excellent collagen formation suppression, cause fewer side-effects and which are safer are obtained.
62 cl, 2717 ex, 432 tbl
FIELD: chemistry.
SUBSTANCE: invention relates to novel bioisosteres of actinonin of general formula (I) , as well as to pharmaceutically acceptable salts thereof and pharmaceutical compositions based on said compounds, with peptide deformylase (PDF) inhibitory activity, as well as to use of the compounds or pharmaceutical compositions based on said compounds to prepare medicinal agents. In general formula (I) R1 is a hydrogen atom, R2 is a hydrogen atom, (C1-C6)alkyl residue, hetero(C1-C6)alkylphenyl residue, where the heteroatom is sulphur, R3 is a hydrogen atom, R4 is (C1-C6)alkyl residue, (C3-C7)cycloalkyl residue, R6 is a hydrogen atom, n is 1, 2 or 3. Values of substitute R5 are given in the formula of invention.
EFFECT: new compounds have useful biological activity.
8 cl, 1 ex
FIELD: pharmacology.
SUBSTANCE: claimed invention relates to compound of formula (I) in which m represents integer number, equal 1 or 2; R1 represents group, selected, in particular from phenyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, thiazolyl, naphtyl, chinolinyl, isochinolinyl, benzisoxazolyl, tienopyridinyl, said group is possibly substituted with one or several groups of R3, similar or different from each other or by group R4, R2 represents group of general formula CHR5CONHR6, R3 represents halogen atom or one of the following groups: piano, nitro, C1-6-alkyl, C1-6-alkoxy, C1-6-trifluoralkyl, C1-6-trifluoralkoxy, benzyloxy, phenyloxy, R4 represents group, selected, in particular from phenyl, benzofuranyl, naphtyl; one orseveral groups R4 can by substituted with one or several groups R3, similar or different from each other; R5 represents hydrogen atom or C1-3-akyl group; R6 represents hydrogen atom or alkyl, C3-7-cycloalkyl or C3-7-cycloalkyl -C1-3-alkylene group; as base, salts of binding of acid, hydrate or solvate. Also invention relates to method of obtaining compound of formula I, its use as medicine and to based on it pharmacological composition.
EFFECT: novel derivatives of 1-pyperazine and 1-homopyperazincarboxilates, useful for prevention or treatment of pathology, in which endogen cannabinoids and/or any other substrates, metabolised by ferment FAAH, participate.
12 cl, 3 tbl, 11 ex
< / BR>where Q1and Q2every means independently hydrogen or halogen;
X is CH2CH or oxygen;
Y represents CR3, CR3R4or (CH2)nwith n = 1-4;
Z denotes CH2CH or oxygen;
R means hydrogen, halogen or alkyl WITH1-4in both cases;
m denotes 1 or 2;
R1means1-6-alkyl, C3-6-cycloalkyl,1-3-haloalkyl,1-6-alkylamino,2-6alkenyl,1-4-alkoxy(C1-4)alkyl, C1-C4-alkylthio(C1-4)alkyl or triptorelin-C1-4;
R2means hydrogen, halogen or C1-4-alkyl; and
R3and R4each independently mean hydrogen or C1-4-alkyl,
containing pharmaceutical compositions for the treatment of sleep disorders, and disorders associated with disturbance of circadian rhythms
ClOCH2COOHH2N< / BR>The claimed connection, its physico-chemical characteristics, method of production and application are not described in literature
OHH2Nwhich can find application in agriculture as a herbicide
CH3OOCCOOHH2Nhave a weed-killing activity
FIELD: medicine, pharmaceutics.
SUBSTANCE: there are described compounds of 3-cyanonaphthalene-1-carboxylic acid and perhydroxyalkylmethylpiperazine of formula
, where R1 means C1-C4alkyl, R2 and R3 mean halogen, R4 is selected from the group consisting of 2-furanyl, 3-furanyl, 2-thiophen, 3-thiophen, phenyl, benzyl, 2-benzofuranyl, etc., R5 is selected from the group consisting of hydrogen and R6, R6 means a subgroup of general formula
which are antagonists of tachykinin receptors. Also, there are described pharmaceutical compositions containing such compounds, and methods for making such compounds and intermediate products for making the compounds according to said methods.
EFFECT: preparation of new compounds.
FIELD: chemistry.
SUBSTANCE: invention relates to compounds of general formula (III): , in which D is a benzene ring, 2-pyridone ring, pyridine ring, benzoxalone ring, benzoxadinone ring or benzimidazole ring; R1 denotes carboxy or hydroxy; R2 independently denotes a halogen atom; alkyl optionally substituted with a halogen atom, aryl or alkylamine; alkynyl, optionally substituted alkoxy; hydroxy; carboxy; alkoxy optionally substituted with phenyl, aromatic heterocyclic ring which denotes a 5-6-member aromatic monocyclic carbocyclic ring containing one or two heteroatoms, independently selected from oxygen and nitrogen atoms; alkylsulphonyl; aryloxy; amino optionally substituted with alkyl; acyl optionally substituted with alkyl or alkyloxy; alkyloxycarbonyl; alkanesulphonyl; arylsulphonyl or alkylcarbamoyl; carbamoyl optionally substituted with alkyl, phenyl, cycloalkyl, acetyl, alkanesulphonyl, heteroarylalkyl, cycloalkylalkyl, heteroaryl which denotes a 5-6-member aromatic monocyclic ring containing one or three heteroatoms independently selected from oxygen and nitrogen atoms, and which is optionally substituted with alkyl or cycloalkyl; acylcyano; nitro, aryl; heteroaryl which denotes a 5-6-member aromatic ring containing one or more heteroatoms independently selected from oxygen, sulphur and nitrogen atoms, and which is optionally substituted with alkyl; alkylsulphonyl; morpholinylsulphonyl; non-aromatic heterocyclic group which denotes a 5-6-member non-aromatic heterocyclic ring containing one or more nitrogen atoms and optionally an oxygen and/or sulphur atom; R3 denotes C1-C6alkyloxy, C1-C6alkylthio; R4 denotes a halogen atom or alkyloxy; R5 denotes alkyl; M denotes sulphonyl; L3 independently denotes alkylene optionally containing one oxygen or nitrogen atom, alkenylene, or -N(R7)-; R7 independently denotes a hydrogen atom, alkyl; Y denotes a single bond or CO; Z denotes CH or N; n equals 0 or 1; p equals 0, 1, or 2; q equals 0 or 1; provided that R1 does not denote carboxy when ring D is a benzene ring, -L3- denotes -(O-alkylene)- and the substitution position of L3 and Y is an ortho-position in ring D; to pharmaceutically acceptable salts thereof. The invention also relates to compounds of formula (IV), a pharmaceutical composition, a method of treating diseases associated with the DP receptor, use of compounds in any of the claims 1-17, as well as compounds of general formula (V).
EFFECT: obtaining novel biologically active compounds having DP receptor antagonist activity.
30 cl, 8 ex, 62 tbl


text:
Calorie Counter - MyFitnessPal
Developer Name
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Update Date
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Apk Version
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Apk Category
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Table Of Contents+
Application Description
Whether you want to lose weight, tone up, get healthy, change your habits, or start a new diet MyFitnessPal has you covered. Our members have lost over 200 million pounds and 88% of people who track for at least 7 …
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text:
we should make a map together. (you map and I can help you change things like viewhands and weapons from other cods)
155 days ago
Lol what perks did you STEAL lol
270 days ago
New YouTube series where I make a map with everyone's reasonable input. Make sure you leave a comment on the video of what to do. This map will be like the early days of WaW modding when bo1 perks were just added. Make sure you subscribe and click the bell to be alert when the next video is releas...
519 days ago
100% ohmergawd
526 days ago
RIP. I kinda wish for more sniper rifles to mess around with like the DSR, but it's fine if there's nothing to be done.
I suggested a DSR during development
528 days ago
I found a cool trick in the taco hell map
explain this trick
530 days ago


text:
Switzerland works out new strategy of cooperation with Moldova for 2018-2021
Switzerland will further support Moldova's reforms agenda through projects in concrete sectors. Presently, the Swiss authorities work out a new strategy of cooperation with Moldova for 2018-2021.
The concerned subject was discussed at a meeting between Parliament Speaker Andrian Candu and Kiev-based Ambassador of the Swiss Confederation to Moldova Guillaume Scheurer, the parliament's communication and public relations department has reported.
Andrian Candu thanked for the punctual and constant support for carrying out the reforms underway. Within the current strategy of cooperation with Moldova for 2014-2017, Switzerland provides Moldova with 55 million Swiss francs, especially in such fields as water and sewerage, health, migration and development, doubling the volume of financial assistance provided in the years before.
"Moldova's citizens have benefited from more useful projects, implemented by the Swiss side. We are interested in their diversification and inclusion in the future strategy of new assistance sectors which are to meet the country's concrete needs, especially in the public administration reform, sustainable development, energy efficiency and renewable energy," Andrian Candu said.
The parliament speaker referred to packages of important laws approved by the parliament or included in its agenda, their enforcement and parliamentary control. The officials exchanged opinions on the social and political developments in Moldova, including the authorities' concrete actions to ensure an attractive business environment for investors, justice reform, reform of the financial and banking sector, electoral legislative framework and public administration reform.
For his part, Ambassador of Switzerland Guillaume Scheurer stressed that efforts for Moldova's modernization must be encouraged and backed.
"Switzerland further takes strong commitments for Moldova's development, with a portfolio of concrete projects for citizens. We will continue supporting you," the Swiss official said.
Switzerland is one of the most important bilateral donors of Moldova. In 2010-2013, 50 projects on technical and humanitarian assistance worth about 30 million Swiss francs were implemented in Moldova with the support of Switzerland in such fields like health and drinking water supply


text:
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Speaking generally, also, the indication is for (tadacip 20 mg dxm) a food containing a low percentage of fat with some increase in the amount of starch and sugar to offset the decrease in fat.
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Last edited 25 Apr 2018
Management contract: tender works contracts
The tender stage is the process of selecting and appointing works contractors. Tendering involves a number of works contracts, contracted by the management contractor. Works contracts may not all be tendered at the same stage, and so this process might be repeated a number of times during the project.
[edit] Starting the work stage.
If they have not already done so, the client may wish to appoint a contract administrator to administer the management contractor's contract. Go to work stage: Management contract: appointment.
The management contractor prepares selection criteria for works contractors and if appropriate pre-qualification questionnaires.
The management contractor and client consider the preferred form of contract, contract conditions and the allocation of risks for works contracts. They then co-ordinate a stage start-up meeting with the consultant team and the client to agree the programme and procedures that will be adopted for tendering.
The client takes advice from the management contractor and decides whether to appoint, or arrange for the appointment of site inspectors.
[edit] Preparing the tender documentation.
NB Throughout this stage, The lead designer co-ordinates completion of statutory approvals and other approvals and negotiations.
The management contractor obtains from the consultant team information for the preparation of the tender documentation, pre-tender estimate, cash flow projection and tender pricing document and prepares the pre-tender estimate, cash flow projection and tender pricing document.
If tendered packages include design by the works contractor, the management contractor prepares 'management contractor's requirements', describing the design services required.
The management contractor co-ordinates a review of the tender documents for the works contracts and issues instructions to make amendments if necessary.
The client reviews the tender documents (including assessment of the pre-tender estimate in relation to the budget) and issues instructions to make further amendments if necessary. The management contractor instigates change control procedures for the tender documents.
[edit] Identifying potential tenderers.
The management contractor prepares a long list of suitable works contractors and issues pre-qualification questionnaires. The management contractor receives completed pre-qualification questionnaires from the long list of potential tenderers and carries out financial checks on potential tenderers (ideally the contract should not be more than 20% of the annual turnover of the potential tenderers).
The management contractor co-ordinates advice on prospective tenderers and prepares a short list of tenderers to present for client comment or approval. The client accepts or alters the initial short list of tenderers and where appropriate the management contractor arranges pre-tender interviews with the initial short list of tenderers.
Following the pre-tender interviews, the management contractor co-ordinates any amendments to the initial short list of tenderers and instructs any amendments to the tender documentation.
[edit] Identifying the preferred tenderer(s).
The management contractor collates tender documents for each of the works contracts and arranges dispatch and return to and from the tenderers.
The management contractor compiles queries from tenderers and co-ordinates responses which should be issued to all tenderers. If necessary, the management contractor arranges mid-tender interviews and/or site visits for the tenderers. If queries from the tenderers or discussions during the mid-tender interviews result in significant clarification of, or changes to, the tender documentation, the management contractor may recommend to the client that the tender period is extended.
The management contractor receives the tenders. They may follow a formal procedure for opening and recording tenders. The management contractor co-ordinates the assessment of the tenders. This may include further interviews.
The management contractor prepares a tender appraisal for the client. NB If the lead consultant disagrees with the management contractor's appraisal, they may submit their own tender appraisal.
The client receives the tender appraisal from the management contractor, and instructs the management contractor to enter into negotiations with the preferred tenderer(s). A reserve tenderer may be retained in the event that negotiations with the preferred tenderer are unsuccessful.
[edit] Entering into negotiations with the preferred tenderer(s).
The management contractor co-ordinates negotiations with the preferred tenderer(s). It is paramount in any negotiation that the individuals at the negotiating table either have authority to fully negotiate terms or make it clear from the start the limits of their authority. This may mean re-convening with the right people empowered to make decisions.
The management contractor co-ordinates the preparation of a tender report. The client considers the tender report and instructs the management contractor if any changes are required to the tender documents. If instructed, the management contractor co-ordinates adjustments to tender documents and requests a revised tender from the preferred tenderer(s).
[edit] Issuing the notice to proceed.
At this stage, the client may negotiate the second stage of the management contractors appointment. This may result in 'definitive particulars' being inserted into the management contract. Any changes to the definitive particulars in the management contract may also require changes to the works contracts.
The client issues a 'notice to proceed' allowing the management contractor to appoint works contractors (as there is more than one works contract, this may already have been done).
[edit] Appointing the works contractor.
The management contractor collates the contract documents and arranges for the printing (engrossment) and execution of two copies, one for themselves and one for the works contractor. This can take place at a specially convened signing meeting. Alternatively, the management contractor might retain one executed contract, with certified copies being issued to the works contractor, this can avoid potential errors in preparing two contracts for execution. The works contractor may be required to provide: a performance bond, warranties, evidence of insurance cover and so on.
The management contractor arranges for copies of the contract documentation (or relevant parts) to be issued to the client and consultant team.
The management contractor informs other tenderers that they have been unsuccessful.
NB. Works contracts may not all be tendered at the same stage, and so this process might be repeated a number of times during the project.
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On the night of April 25, , a series of high explosive bombs, showers of incendiaries, and a parachute mine dropped from the darkened skies. The youngest victim was nine-week-old Joseph Reed, the oldest was year-old Isabella Harrison. Bodies were still being recovered five days later. Those who remained unidentified were buried in a common grave in Heaton Cemetery. On April 16, , the Germans launched heavy air raids targeting the newly commissioned aircraft carrier HMS Victorious which was due to steam out of the Tyne.
On the night of October 4, , a German plane dropped its bombs on to the Market Place and nearby rows of terraced houses and swept the streets with machine gun fire. Meanwhile, a 60ft pillar of flame shot into the sky from a fractured gas main adding to the apocalyptic scenes. More than 2, folk were made homeless. One little girl was discovered wandering the streets in her pyjamas, sobbing uncontrollably. Her mother had been killed. The night of May 3, , witnessed one of the most the most shocking incidents of death and destruction ever to affect the North East. We learned a great deal about the history of Dutch resistance and got the best fries in Amsterdam.
Thank you for a great morning. Laura was an amazing local guide. She took me and my husband around in Amsterdam and we had a wonderful tour. She knew the history and the important things about the city. A great 3 hours with a great guide Wonderful trip. A perfect day in Ansterdam! We just finished our 2 day tour with Laura and it was wonderful!! From the hidden courtyards and tilted houses to the best places for fried fish or pickled herring and absolutely delicious apple pie both days were packed with so much interesting information.
We thoroughly enjoyed it. My 82 year old parent's were with us and we appreciated the slower pace, always taking care to ask if they needed a rest.
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We throughly enjoyed our tour with Laura Maria yesterday. She is so knowledgeable, friendly and calm. We all felt so relaxed in her company and she tailored it perfectly to our requirements. Our tour felt like walking around town with a good friend.
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She took us to eat fantastic Flemish fries and a delicious cookie. I would recommend her for sure! Thank you Laura! Excellent Amsterdam Knowledge! We loved Laura Maria! As a former resident of the area, she knew all the ins and outs of all the little side streets we may have missed. I think we covered them all. She was also very informative about the complete history of the area up to the present time.
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She was one of our favorite tour guides on our trip. The food in Amsterdam was fantastic, and she did a great job sharing stories about living there. She modified the tour slightly to our tastes because we had tried croquettes that morning before going on the tour. She was knowledgeable and shared a little history of Amsterdam with us and even shared about her life there. If you are looking for someone laid back and easy to talk to, book with Laura. Highly recommend! Laura Maria give us an excellent walking tour of Amsterdam.
Meeting instructions were easy to follow and Laura was very punctual. She is friendly, has very good English, explains everything clearly and answered all questions really well. She often asked for feedback, if we understood or wanted better information, and made good suggestions about sites on the way. A small group format works really well in a large city and we felt we got to see a lot of sites in a short period of time especially as we could all walk quite quickly.
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The Loss of a Beloved Pet: 6 Ways to Stay Stable
At the difficult time of losing a pet, it's important to have a plan in place to prevent bipolar disorder symptoms from taking hold.
My beloved kitty Bibi is gone. I was ready for her death and want to share with you what I'm doing in order to keep myself stable while going through the grief of losing one of my best friends.
Do you have a pet you love? Many of us find such comfort in our wonderful animal companions.
This next question is harder: As a person with bipolar, do you have a plan in place for real loss? In other words, are you ready for the loss of a beloved pet? Especially if this animal helps with your symptoms? I used to call Bibi my depression companion. What a lovely soul in a beautiful body!
Now she is a soul.
The death of a pet is a bipolar disorder trigger. We need a plan in place for when loss of a pet happens. It can be sudden or it can be drawn out as it was with Bibi. We need a plan now that we put into place when the news that a pet is ill or a sudden death happens.
When I heard Bibi had cancer, I had to think of many things outside of my grief. I made sure that I honored her every day she had left. But at the same time, I had to take care of my bipolar disorder. My motto is Treat Bipolar First. It is the only way I can move through life without getting sick.
I wrote the following the day after Bibi died.
I hope it helps you if you are going through something similar. And, if you have a pet and want to make sure you stay well enough to grieve and feel the normal sadness we all experience with loss, I hope you will start a plan now that can be in place when the death happens.
The hardest part of this by far was not knowing how her death might affect my bipolar.
On the day she died, I could not sleep. I wanted to write about her in my journal and remember her and cry. All natural behaviors. What was not natural was the fact that it was past midnight. At 1 AM, I realized it could be dangerous for my bipolar as I could easily not sleep at all.
I decided I could love her and think of her the next day. I forced myself to sleep.
I took extra sleep meds and got 8 hours. It wasn't easy, but I did it. I had a plan in place for what I would do if I could tell that my sadness and grief were morphing into mania or depression, and I used it.
Please think ahead….
What is your plan if your kitty gets sick? What is your plan if your best friend who happens to be a dog, simply gets older as all animals do and his time is near?
I want us to prepare for bipolar disorder triggers so that when they arrive, we know what to do.
Here is a short list of what I did to make Bibi's death as gentle as possible for my brain:
1. When I realized that my sleep would be affected, I asked my mom to help with her care-taking. We were a team in this until the end. I could not stay up at night with Bibi. The guilt was enormous at first, but everyone helped. It also helped that she had a very compassionate vet.
2. I imagined life without her. I thought of what I might feel and opened myself to what might show up in terms of bipolar. Yes, I did this before she died.
3. I regulated my sleep. This meant sleeping in for two more hours than usual the day she died. It would be hard to do this if I were at a work place, but I have my own business, so it is possible. If you need this and do work with set hours, take sick time.
4. I decided to fully feel everything, but gave myself a time limit for grief. If I don't do this, it will spiral into depression. This means I can cry naturally, but I will not let myself cry for five hours straight for example. When the panic attacks showed up, I felt them, did my breathing, talked to myself and worked through them. It's so much easier to do this when you plan ahead.
5. I told my friends that Bibi was dying and asked for help.
6. When it was time, I took her to the vet and had a loving goodbye.
I want to learn from this experience so that when another pet or someone I love dies, I will know what works. I am not doing anything to push down my feelings or have less grief. That is normal.
But I am doing everything I can not to get sick. Depression is knocking on the door. I will not let depression in this hotel!
What is your plan? If it is very painful to think about this, I see that as a positive. It means you will need to plan ahead or the grief might be too much if something happens.
Let's all have a plan ready for when a beloved pet leaves our lives.
When we manage bipolar, we can have the space needed to remember and celebrate all of the joy our beloved pet brought into our lives


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