The effect of thyroid hormone on the absorption of L-proline, chloramphenicol and digitoxin

Using the method of the perfused small intestine preparation in situ, the influence of triiodothyronine on the absorption was investigated. The absorptions of L-proline and digitoxin were disturbed by the thyroid hormone in different ways, in contrast to chloramphenicol, where it is unaltered. The effects of triiodothyronine on the absorption of these substances are dose dependently different. Obviously the thyroid hormone can influence the absorption of proline and digitoxin in both ways, increase or decrease. The behaviour of digitoxin different from that of chloramphenicol points to this drug making use of active mechanisms concerned in the absorption.     

Angiotensin II induces a rapid and transient increase of reactive oxygen species

Vascular smooth muscle cells (VSMC) exhibit a hypertrophic and contractile response after angiotensin II (Ang II) treatment, and the NADH/NADPH oxidase-dependent synthesis of hydrogen peroxide (H(2)O(2)) seems to play a central role in these responses. Present experiments were designed to analyze the mechanisms responsible for the rapid changes induced by Ang II in the intracellular H(2)O(2) concentration in VSMC. Ang II induced a quick and transient increase of dichlorodihydrofluorescein (DCHF) fluorescence in VSMC, an effect that was completely abolished by catalase and by diethyldithiocarbamate, a cell-permeable superoxide dismutase inhibitor. Losartan and pertussis toxin prevented the stimulatory effect of Ang II. Both diphenylene iodonium (NADH/NADPH oxidase blocker) and 3-(4-octadecylbenzoyl)acrylic acid (phospholipase A2 blocker) inhibited the changes in DCHF fluorescence induced by Ang II, in a dose-dependent fashion, and the effects of both inhibitors were additive. These data demonstrate that Ang II induces a very quick and transient increase of H(2)O(2) in VSMC. This effect depends on the receptor type 1, is linked to a G protein, and involves both NADH/NADPH oxidase and phospholipase A2 activation. The mechanism may be related to the previously proposed role of H(2)O(2) in the genesis of the Ang II-induced cell contraction.     

Anti-inflammatory effect of aqueous extracts of spent Pleurotus ostreatus substrates in mouse ears treated with 12-O-tetradecanoylphorbol-13-acetate

Aims:

To evaluate the application of spent Pleurotus ostreatus substrates, enriched or not with medicinal herbs, as a source of anti-inflammatory compounds.

Subjects and Methods:

P. ostreatus was cultivated on five different substrates: Barley straw (BS) and BS combined 80:20 with medicinal herbs (Chenopodium ambrosioides L. [BS/CA], Rosmarinus officinalis L. [BS/RO], Litsea glaucescens Kunth [BS/LG], and Tagetes lucida Cav. [BS/TL]). The anti-inflammatory activity of aqueous extracts of spent mushroom substrates (SMSs) (4 mg/ear) was studied using an acute inflammation model in the mouse ear induced with 2.5 μg/ear 12-O-tetradecanoylphorbol13-acetate (TPA).

Results:

Groups treated with BS/CA, BS/RO, and BS/LG aqueous extracts exhibited the best anti-inflammatory activity (94.0% ± 5.5%, 92.9% ± 0.6%, and 90.4% ± 5.0% inhibition of auricular edema [IAO], respectively), and these effects were significantly different (P < 0.05) from that of the positive control indomethacin (0.5 mg/ear). BS/TL and BS were also able to reduce TPA-induced inflammation but to a lesser extent (70.0% ± 6.7% and 43.5% ± 6.6% IAO, respectively).

Conclusions:

Spent P. ostreatus substrate of BS possesses a slight anti-inflammatory effect. The addition of CA L. to mushroom substrate showed a slightly synergistic effect while RO L. had an additive effect. In addition, LG Kunth and TL Cav. enhanced the anti-inflammatory effect of SMS. However, to determine whether there is a synergistic or additive effect, it is necessary to determine the anti-inflammatory effect of each medicinal herb.KEY WORDS: Anti-inflammatory activity, medicinal herbs, Pleurotus ostreatus, spent mushroom substrate     

Utero-cutaneous fistula: a case report and literature review

Utero-cutaneous fistula is a rare clinical entity with less than 15 cases reported worldwide in the last 20 years and this is the first case reported in our country. In this article we review the worldwide literature addressing this condition and present the first case reported in México and the first case reported worldwide in which the fistula is demonstrated using a combination of fistulogram and CT.     

Design and biological evaluation of 99mTc-N2S2-Tat(49–57)-c(RGDyK): A hybrid radiopharmaceutical for tumors expressing α(v)β(3) integrins

The α(ν)β(3) integrin is over-expressed in the tumor neovasculature and the tumor cells of glioblastomas. The HIV Tat-derived peptide has been used to deliver various cargos into cells. The aim of this research was to synthesize and assess the in vitro and in vivo uptake of ^99mTc-N₂S₂-Tat(49–57)-c(RGDyK) (^99mTc-Tat-RGD) in α(ν)β(3) integrin positive cancer cells and compare it to that of a conventional ^99mTc-RGD peptide (^99mTc-EDDA/HYNIC-E-[c(RGDfK)]₂). Methods: The c(RGDyK) peptide was conjugated to a maleimidopropionyl (MP) moiety through Lys, and the MP group was used as the branch position to form a thioether with the Cys¹² side chain of the Tat(49–57)-spacer-N₂S₂ peptide. ^99mTc-Tat-RGD was prepared, and stability studies were carried out by size exclusion HPLC analyses in human serum. The in vitro affinity for α(v)β(3) integrin was determined by a competitive binding assay. In vitro internalization was determined using glioblastoma C6 cells. Biodistribution studies were accomplished in athymic mice with C6 induced tumors that had blocked and unblocked receptors. Images were obtained using a micro-SPECT/CT. Results: ^99mTc-Tat-RGD was obtained with a radiochemical purity higher than 95%, as determined by radio-HPLC and ITLC-SG analyses. Protein binding was 15.7% for ^99mTc-Tat-RGD and 5.6% for ^99mTc-RGD. The IC₅₀ values were 6.7 nM (^99mTc-Tat-RGD) and 4.6 nM (^99mTc-RGD). Internalization in C6 cells was higher in ^99mTc-Tat-RGD (37.5%) than in ^99mTc-RGD (10%). Biodistribution studies and in vivo micro-SPECT/CT images in mice showed higher tumor uptake for ^99mTc-Tat-RGD (6.98% ± 1.34% ID/g at 3 h) than that of ^99mTc-RGD (3.72% ± 0.52% ID/g at 3 h) with specific recognition for α(v)β(3) integrins. Conclusions: Because of the significant cell internalization (Auger and internal conversion electrons) and specific recognition for α(v)β(3) integrins, the hybrid ^99mTc-N₂S₂-Tat(49–57)-c(RGDyK) radiopharmaceutical is potentially useful for the imaging and possible therapy of tumors expressing α(v)β(3) integrins.     

Fundamental Causes of Colorectal Cancer Mortality in the United States: Understanding the Importance of Socioeconomic Status in Creating Inequality in Mortality

Objectives. We used the fundamental cause hypothesis as a framework for understanding the creation of health disparities in colorectal cancer mortality in the United States from 1968 to 2005.Methods. We used negative binomial regression to analyze trends in county-level gender-, race-, and age-adjusted colorectal cancer mortality rates among individuals aged 35 years or older.Results. Prior to 1980, there was a stable gradient in colorectal cancer mortality, with people living in counties of higher socioeconomic status (SES) being at greater risk than people living in lower SES counties. Beginning in 1980, this gradient began to narrow and then reversed as people living in higher SES counties experienced greater reductions in colorectal cancer mortality than those in lower SES counties.Conclusions. Our findings support the fundamental cause hypothesis: once knowledge about prevention and treatment of colorectal cancer became available, social and economic resources became increasingly important in influencing mortality rates.Colorectal cancer is the third leading cause of cancer-related deaths among men and women in the United States.1 In 2010 an estimated 142 570 people in the United States were diagnosed with colorectal cancer, and 50 370 people died as a result of the disease in the same year.2 Over the past 30 years, there have been significant advances in the prevention of colorectal cancer, with reductions in mortality rates due predominantly to improvements in screening and early cancer detection.One of the primary goals of colorectal cancer screening is to reduce mortality by promoting early detection of the disease. Methods used to detect colorectal cancer also aid physicians in the identification and removal of adenomas, which can give rise to colorectal cancer.3 However, because of the unequal distribution of social and economic resources in our society, knowledge about prevention and access to treatments for colorectal cancer is not universal but, rather, is unevenly distributed along the typical social cleavages of race, class, and gender. Thus, social inequalities in colorectal cancer outcomes remain remarkably evident even in an era of successful prevention and treatment strategies.4To gain a more thorough understanding of how existing social inequalities have slowed the decline in mortality attributable to colorectal cancer, we used the “fundamental cause” hypothesis to analyze almost 40 years of US death certificate data. This theoretical construct, first put forth by Link and Phelan,5 stems from the observation that adverse social conditions are repeatedly associated with higher levels of mortality in distinctly different eras and settings.5–9 According to the hypothesis, the association between socioeconomic status (SES) and mortality endures because access to resources such as knowledge, money, power, prestige, and beneficial social connections influences the extent to which people are able to avoid disease and death as well as harness protective factors that can be used to reduce morbidity and mortality.The fundamental cause hypothesis further predicts that as individuals learn how to better prevent or treat diseases, benefits stemming from these newfound abilities will not be distributed uniformly throughout a population. Instead, they will be realized to a greater extent by those who are less likely to face discrimination and stigma and are more likely to have access to socioeconomic resources such as education, money, and information,7 thus resulting in health disparities along common social divisions such as SES and race. According to the hypothesis, more advantaged individuals, relative to their less advantaged counterparts, are poised to disproportionately gain from new health-enhancing capabilities, which may translate to earlier and more rapid reductions in mortality rates.We examined SES inequalities in colorectal cancer mortality in light of major advances in preventing or delaying death, advances predominantly due to improvements in screening and associated policy recommendations. Although colorectal cancer has been surgically treated for more than a century, an emphasis on the prevention of colorectal cancer through widespread screening has become routine only in the past 30 years. In July 1980, the American Cancer Society (ACS) first published recommendations for colorectal cancer screening.10 In 1997, the US Multi-Society Task Force (MSTF), assembled by the US Agency for Health Care Policy Research in conjunction with the American Gastroenterological Association, published its first guidelines for screening for colorectal cancer.11The MSTF guidelines recommended that everyone with risk factors such as age (≥ 50 years), family or personal history of colorectal cancer, history of inflammatory bowel disease, chronic ulcerative colitis, adenomatous polyposis, juvenile polyposis, and hereditary nonpolyposis colorectal cancer be screened. Furthermore, following a positive screen, physicians should conduct a diagnostic evaluation of the colon and rectum, use recommended treatments (including the removal of adenomatous polyps), and consider follow-up surveillance after treatment. In 1997, influenced by MSTF’s recommendations, ACS revised its 1980 guidelines to include recommendations stratified by level of risk of developing colorectal cancer.11 Since then, both ACS and MSTF have issued updates on a regular basis.12The 1997 ACS guidelines recommended that all individuals at an average level of risk begin colorectal cancer screening at the age of 50 years. Individuals at moderate risk, based on a personal or family diagnosis of gastrointestinal adenomatous polyps or colorectal cancer, were recommended to initiate screening at the time of onset, the age of 40 years, or 10 years before the youngest case in the family, whichever was earlier. High-risk individuals with hereditary predispositions to colorectal cancer or a personal diagnosis of inflammatory bowel disease were recommended to initiate screening at puberty, at the age of 21 years, or 8 to 15 years after the onset of inflammatory bowel disease, depending on their individual risk factors.11According to the fundamental cause hypothesis, developments in colorectal cancer screening, such as clearly stated, evidence-based guidelines and their widespread dissemination, will benefit people of high SES more than their low-SES counterparts, thereby creating new health disparities or exacerbating existing disparities over time. Specifically, we expected individuals living in high-SES locales to benefit from recent developments in colorectal cancer screening, beginning with the release of the first colorectal cancer screening recommendations by ACS. Furthermore, given that socioeconomic inequalities are reproduced and often accentuated over time, we expected the association between SES and colorectal cancer mortality to increase over time.     

Suddenly,a Carriage Appears: Social Support Needs of Latina Breast Cancer Survivors

Through focus groups and individual interviews, data were gathered on the emotional, informational, and instrumental support needs of 22 immigrant Latina women. A thematic analysis revealed that participants who perceived to receive social support reported less psychological distress and better adjustment to breast cancer than those who did not perceive this support. Types and sources of support varied across survivorship stages. Many needs were related to financial, linguistic, and cultural barriers participants encountered in the course of the disease. Based on the findings, we conclude with several clinical recommendations to improve the quality of life in this medically underserved population.     

Vitamin D Treatment Prevents Uremia-Induced Reductions in Aortic microRNA-145 Attenuating Osteogenic Differentiation despite Hyperphosphatemia

In chronic kidney disease, systemic inflammation and high serum phosphate (P) promote the de-differentiation of vascular smooth muscle cells (VSMC) to osteoblast-like cells, increasing the propensity for medial calcification and cardiovascular mortality. Vascular microRNA-145 (miR-145) content is essential to maintain VSMC contractile phenotype. Because vitamin D induces aortic miR-145, uremia and high serum P reduce it and miR-145 directly targets osteogenic osterix in osteoblasts, this study evaluated a potential causal link between vascular miR-145 reductions and osterix-driven osteogenic differentiation and its counter-regulation by vitamin D. Studies in aortic rings from normal rats and in the rat aortic VSMC line A7r5 exposed to calcifying conditions corroborated that miR-145 reductions were associated with decreases in contractile markers and increases in osteogenic differentiation and calcium (Ca) deposition. Furthermore, miR-145 silencing enhanced Ca deposition in A7r5 cells exposed to calcifying conditions, while miR-145 overexpression attenuated it, partly through increasing α-actin levels and reducing osterix-driven osteogenic differentiation. In mice, 14 weeks after the induction of renal mass reduction, both aortic miR-145 and α-actin mRNA decreased by 80% without significant elevations in osterix or Ca deposition. Vitamin D treatment from week 8 to 14 fully prevented the reductions in aortic miR-145 and attenuated by 50% the decreases in α-actin, despite uremia-induced hyperphosphatemia. In conclusion, vitamin D was able to prevent the reductions in aortic miR-145 and α-actin content induced by uremia, reducing the alterations in vascular contractility and osteogenic differentiation despite hyperphosphatemia.