Observations on the Etiology and Therapy of “Brittle” Diabetes

Salient aspects of prolonged metabolic studies on seven excessively labile diabetic patients and a review of the literature concerning causation and therapy of brittle diabetes are presented. Brittleness is redefined as “a syndrome of excessive insulin-sensitivity and ketosis-proneness manifested by extreme and unexplainable short-term and long-term fluctuations in the parameters of the disease”. Evidence on the causation of hyperlability points to dysfunction of plasma-protein transport and of hepatic and peripheral tissue metabolism of insulin. No objectively demonstrable complete and lasting stabilization was possible by means of any antidiabetic or adjunctive therapeutic measures. However, achievement of quantitative improvement in the accuracy of regulation of diabetes and moderation in deviations from the acceptable range of parameters were feasible. To this end, therapy recommended for everyday use incorporates the following principles found to be most helpful in following the oscillations of the disease on the research ward: flexibility in the plan of therapy; accuracy, especially in timing of therapeutic events; and employment of an insulin program best suited to the patient''s needs and comfort.     

The ecology of a late Visean forest at Catcraig (East Lothian,Scotland) based on multiproxy study of paleosol and root-casts

The Middle Longcraig Limestone (late Visean) at Catcraig, Scotland, is densely covered with large (about 1 m in diameter) hollows, which are surrounded by numerous fossilized roots. The latter represent the positions of tree-sized plants belonging to a fossil forest. This paper aims to reconstruct its ecology based on paleosol properties, size and spatial distribution of root-casts, rooting system morphology and characteristics of coalified plant remnants. The obtained data are consistent with the supposition that the Visean peat wetland forest of Catcraig represents a Cordaitalean dominated community composed of mono-sized, most probably, even-aged giant trees. The peaty paleosol (Histosol) contains pyrite and siderite, indicating reducing and acidic conditions, whilst the abundant presence of gypsum testifies periods of elevated salinity. The adaptation of trees to such conditions is supported by morphologically evident large root mass (typically more than 1000 individual roots per cast). Good preservation of plant tissues in peat, in addition to other paleosol and rooting system characteristics allow us to conclude that the trees occupied seacoast settings or lagoons, which were not permanently flooded.     

5-alkylvinyl-1,2,4-triazole nucleosides: Synthesis and biological evaluation

Abstract

Some 5-substituted ribavirin analogues have a high antiviral and anticancer activity, but their mechanisms of action are obviously not the same as their parent compound. The SAR studies performed on 3 (5)-substituted 1,2,4-triazole nucleosides have shown a high dependency between the structure of the 3 (5)-substituent and the level of antiviral/anticancer activity. The most active substances of the row contain coplanar with the 1,2,4-triazole ring aromatic substituent which is connected by a rigid ethynyl bond. However, the compounds with the trans-vinyl linker also had antiviral activity. We decided to study the antitumor activity of ribavirin analogues with alkyl/aryl vinyl substituents in the 5th position of the 1,2,4-triazole ring. Protected nucleoside analogues with various 5-alkylvinyl substituents were obtained by Horner-Wadsworth-Emmons reaction from the common precursor and converted to the nucleosides. Arylvinyl nucleosides were synthesised according the reported procedures. All compounds did not show significant antiproliferative activity on several tumour cell lines. Coplanar aromatic motif in the 5-substituent for the anticancer activity manifestation was confirmed.     

Leprosy in a prison population: A new active search strategy and a prospective clinical analysis

BackgroundThis study evaluates an active search strategy for leprosy diagnosis based on responses to a Leprosy Suspicion Questionnaire (LSQ), and analyzing the clinical, immunoepidemiological and follow-up aspects for individuals living in a prison population.MethodsA cross-sectional study based on a questionnaire posing 14 questions about leprosy symptoms and signs that was distributed to 1,400 prisoners. This was followed by dermatoneurological examination, anti-PGL-I serology and RLEP-PCR. Those without leprosy were placed in the Non-leprosy Group (NLG, n = 1,216) and those diagnosed with clinical symptoms of leprosy were placed in the Leprosy Group (LG, n = 34).FindingsIn total, 896 LSQ were returned (64%), and 187 (20.9%) of the responses were deemed as positive for signs/symptoms, answering 2.7 questions on average. Clinically, 1,250 (89.3%) of the prisoners were evaluated resulting in the diagnosis of 34 new cases (LG), based on well-accepted clinical signs and symptoms, a new case detection rate of 2.7% within this population, while the NLG were comprised of 1,216 individuals. The confinement time medians were 39 months in the LG while it was 36 months in the NLG (p>0.05). The 31 leprosy cases who responded to the questionnaire (LSQ+) had an average of 1.5 responses. The symptoms “anesthetized skin area” and “pain in nerves” were most commonly mentioned in the LG while “tingling, numbness in the hands/feet”, “sensation of pricks and needles”, “pain in nerves” and “spots on the skin” responses were found in more than 30% of questionnaires in the NLG. Clinically, 88.2% had dysesthetic macular skin lesions and 97.1% presented some peripheral nerve impairment, 71.9% with some degree of disability. All cases were multibacillary, confirming a late diagnosis. Anti-PGL-I results in the LG were higher than in the NLG (p<0.0001), while the RLEP-PCR was positive in 11.8% of the patients.InterpretationOur findings within the penitentiary demonstrated a hidden prevalence of leprosy, although the individuals diagnosed were likely infected while living in their former communities and not as a result of exposure in the prison. The LSQ proved to be an important screening tool to help identify leprosy cases in prisons.     

Catalytic antibodies in the bone marrow and other organs of Th mice during spontaneous development of experimental autoimmune encephalomyelitis associated with cell differentiation

Exact mechanisms of autoimmune disease development are still yet unknown. However, it is known that the development of autoimmune diseases is associated with defects in the immune system, namely, the violation of the bone marrow hematopoietic stem cells (HSCs) differentiation profiles. Different characteristics of autoimmune reaction development in experimental autoimmune encephalomyelitis (EAE) prone Th mice characterizing T-lymphocytes response were analyzed using standard approaches. Profiles of several HSCs differentiation of bone marrow (BFU-E, CFU-E, CFU-GM, CFU-GEMM, T- and B-lymphocytes) of Th male and female mice during spontaneous development of EAE were noticeably different. Patterns of total lymphocytes, B- and T-cells proliferation in several different organs (bone marrow, blood, spleen, thymus, and lymph nodes) were also remarkably different. In addition, there were in time noticeable differences in their changes for some organs of male and female mice. Characters of changes in the profiles of CD4 and CD8 cells proliferation in some organs not always coincide with those for total T lymphocytes. The changes in the differentiation profiles of HSCs and the level of lymphocytes proliferation in the bone marrow and other organs were associated with the increase in the concentration of antibodies against DNA, myelin basic protein, and myelin oligodendrocyte glycoprotein, and catalytic antibodies hydrolyzing these substrates. Despite some differences in changes in the analyzed parameters, in general, the spontaneous development of EAE in male and female mice occurs to some extent in a comparable way.

     

Versatile Solid Supports for Oligonucleotide Synthesis that Incorporate Urea Bridge

The universal solid support, USIII, representing a new and improved version of commercial USII, as well as 2 ′-deoxynucleoside and 2 ′-deoxy-2 ′-fluoronucleoside bound supports, incorporating a labile phenoxyacetyl fragment, was synthesized by an aminomethyl polystyrene carbamoylation with corresponding azides in the presence of aqueous triethylammonium bicarbonate. All three solid phases incorporate a stable urea tether, thus bridging the polymer and functional linker. These new matrices proved to be potent solid phases for the synthesis of DNA, RNA, or modified oligonucleotides as well as randomized mixed 2 ′-ribo/2 ′-deoxy-2 ′-fluoro-RNA libraries and/or DNA libraries, randomized with trinucleotides (codons).     

Three new species of the genus Probles F?rster (Hymenoptera,Ichneumonidae, Tersilochinae) from?South Korea

Three closely related species of the genus Probles Förster, P. fulgida sp. n., P. korusa sp. n. and P. rukora sp. n., belong to the subgenus Euporizon Horstmann and differ from other Palearctic species of the genus by a combination of long and apically weakly sinuate ovipositor and short temple. These three species are assigned to a newly designated fulgida species-group, and a portion of the key for identification of this species-group is provided. Based on the shape of the ovipositor apex, the fulgida species-group resemble members of the subgenus Microdiaparsis Horstmann but are distinct in having a much shorter temple.