Skin disorders and thyroid diseases.

Thyroid disorders have a high prevalence in medical practice; they are associated with a wide range of diseases with which they may or may not share etiological factors. One of the organs which best show this wide range of clinical signs is the skin. This review is an attempt to approach most of the dermopathies reflecting several degrees of harmfulness, coming directly or indirectly from thyroid abnormalities, as well as to update current knowledge on the relationship between the thyroid and skin. We have proposed a primary classification of skin disorders, regarding thyroid involvement, into two main groups: 1) dermopathies associated with thyroid abnormalities, mainly with autoimmune thyroid diseases, like melasma, vitiligo, Sjogren's syndrome, alopecia, idiopathic hirsutism, pre-menstrual acne, bullous diseases, connective tissue diseases, hamartoma syndrome, atopy, leprosy and DiGeorge anomaly; and 2) dermopathies depending on the nature of the thyroid disorder, in which the evolution and outcome of the skin disorder depend on the thyroidal treatment in most cases, such as trophism and skin blood flow, myxedema, alopecia, onychodystrophy, hypo- and hyperhidrosis, xanthomas, intraepidermal bullae, carotenodermia, pruritus, flushing, pyodermitis, palmoplantar keratoderma, ecchymosis, etc. In some other cases, the skin disease which developed as a consequence of the thyroid abnormality can remain unaltered despite functional treatment of the thyroid problem, such as pretibial myxedema, thyroid acropachy and some cutaneous manifestations of multiple endocrine neoplasia types 2A and 2B.     

Indications and outcome of pediatric tracheostomy: results from a Nigerian tertiary hospital

Background  

There is a change in the concept of pediatric tracheostomy. This study investigates the indications and outcomes of pediatric tracheostomy in a Nigerian teaching hospital finding out whether there is also a change in the trend in our environment as compared to other centers.     

Use of alcoholic beverages in VA medical centers

Background  

Benzodiazepines are the first-line choice for the treatment of alcohol withdrawal syndrome. However, several hospitals continue to provide alcoholic beverages through their formulary for the treatment of alcohol withdrawal. While there are data on the prevalence of this practice in academic medical centers, there are no data on the availability of alcoholic beverages at the formularies of the hospitals operated by the department of Veteran's Affairs.     

Digestibility of resistant starch containing preparations using two in vitro models

Background Resistant starch (RS) is known for potential health benefits in the human colon. To investigate these positive effects it is important to be able to predict the amount, and the structure of starch reaching the large intestine. Aim of the study The aim of this study was to compare two different in vitro models simulating the digestibility of two RS containing preparations. Methods The substrates, high amylose maize (HAM) containing RS type 2, and retrograded long chain tapioca maltodextrins (RTmd) containing RS type 3 were in vitro digested using a batch and a dynamic model, respectively. Both preparations were characterized before and after digestion by using X-Ray and DSC, and by measuring their total starch, RS and protein contents. Results Using both digestion models, 60-61 g/100 g of RTmd turned out to be indigestible, which is very well in accordance with 59 g/100 g found in vivo after feeding RTmd to ileostomy patients. In contrast, dynamic and batch in vitro digestion experiments using HAM as a substrate led to 58 g/100 g and 66 g/100 g RS recovery. The degradability of HAM is more affected by differences in experimental parameters compared to RTmd. The main variations between the two in vitro digestion methods are the enzyme preparations used, incubation times and mechanical stress exerted on the substrate. However, for both preparations dynamically digested fractions led to lower amounts of analytically RS and a lower crystallinity. Conclusions The two in vitro digestion methods used attacked the starch molecules differently, which influenced starch digestibility of HAM but not of RTmd.     

Preclinical Profile of BI 224436, a Novel HIV-1 Non-Catalytic-Site Integrase Inhibitor

BI 224436 is an HIV-1 integrase inhibitor with effective antiviral activity that acts through a mechanism that is distinct from that of integrase strand transfer inhibitors (INSTIs). This 3-quinolineacetic acid derivative series was identified using an enzymatic integrase long terminal repeat (LTR) DNA 3′-processing assay. A combination of medicinal chemistry, parallel synthesis, and structure-guided drug design led to the identification of BI 224436 as a candidate for preclinical profiling. It has antiviral 50% effective concentrations (EC₅₀s) of <15 nM against different HIV-1 laboratory strains and cellular cytotoxicity of >90 μM. BI 224436 also has a low, ∼2.1-fold decrease in antiviral potency in the presence of 50% human serum and, by virtue of a steep dose-response curve slope, exhibits serum-shifted EC₉₅ values ranging between 22 and 75 nM. Passage of virus in the presence of inhibitor selected for either A128T, A128N, or L102F primary resistance substitutions, all mapping to a conserved allosteric pocket on the catalytic core of integrase. BI 224436 also retains full antiviral activity against recombinant viruses encoding INSTI resistance substitutions N155S, Q148H, and E92Q. In drug combination studies performed in cellular antiviral assays, BI 224436 displays an additive effect in combination with most approved antiretrovirals, including INSTIs. BI 224436 has drug-like in vitro absorption, distribution, metabolism, and excretion (ADME) properties, including Caco-2 cell permeability, solubility, and low cytochrome P450 inhibition. It exhibited excellent pharmacokinetic profiles in rat (clearance as a percentage of hepatic flow [CL], 0.7%; bioavailability [F], 54%), monkey (CL, 23%; F, 82%), and dog (CL, 8%; F, 81%). Based on the excellent biological and pharmacokinetic profile, BI 224436 was advanced into phase 1 clinical trials.