Assessment of left ventricular geometry in normotensive type II diabetic patients.

Background: Abnormalities of glucose metabolism are associated with abnormal left ventricular geometry (LV) independent of atherosclerosis. Abnormal LV geometry, a predictor of premature cardiovascular events, indicates presence of subclinical target organ damages. Screening for abnormal LV geometry in diseases of abnormal glucose metabolism is desirable as part of their management protocol. Aim: To assess the left ventricular geometry in normotensive type II diabetic patients. Cross-sectional, descriptive, hospital-based study. One hundred normotensive type II diabetic patients drawn from the Endocrinology and Family Medicine Clinics of a tertiary hospital were age- and gender-matched with 100 apparently healthy controls. Participants meeting the criteria and informed consent proceeded for clinical evaluation, biochemical assessment, electrocardiography, and echocardiography using the American Society of Echocardiography guideline. Materials and Methods: Data were analyzed using the Statistical Package for Social Sciences [SPSS] version 25.0 (Chicago Illinois, USA). Results: Mean age of study and control groups was (55.56 ± 9.89 versus 55.47 ± 10.7) years (χ2 = 0.062, P = 0.951). The mean duration of diabetes illness was 6.57 ± 6.26 years. Prevalence of abnormal LV geometry was 51% (study) versus 18% (control) FT, P < 0.001). Concentric remodeling was the predominant geometry in 36% of study versus 11% of controls, followed by eccentric hypertrophy in 11% (study) versus 4% (control) and concentric hypertrophy in 4% (study) versus 3% (control). Geometry was normal in 49% of study against 82% in the controls (FT, P < 0.001). Significant association existed between LV geometry and duration of diabetes (χ2 = 10.793, P = 0.005). Conclusion: Abnormal LV geometry is highly prevalent in normotensive diabetic patients.

The Prevalence and Pattern of Thyroid Dysfunction in HAART-Naïve HIV Patients in Enugu, Nigeria: A Cross-Sectional Comparative Study.

BACKGROUND: HIV/AIDS is a multi-system disease that has been associated with several endocrinopathies including thyroid dysfunction. Thyroid dysfunction in patients with HIV/AIDS, among other factors, may arise from the direct cytopathic effects of HIV on the thyroid gland in addition to the adverse effects of highly active anti-retroviral drugs (HAART). STUDY OBJECTIVE: The study aimed to determine the prevalence and pattern of thyroid dysfunction in HAART naïve HIV patients in Enugu. MATERIALS & METHODS: Study was cross sectional, casecontrol based, involving 250 HAART naïve HIV sero-positive patients and 250 HIV sero-negative subjects. Anthropometric measurements and physical examination were done. Assay for fT3, fT4, TSH (for thyroid function) was done using the Enzyme Linked Immunoassay (ELISA) method. Data was analyzed using the Statistical Package for Social Sciences (SPSS) version 23. RESULTS: The HAART naïve sero-positive cohorts comprised 112 males and 138 females while the control subjects consisted of 125 males and 125 females. Mean ages (years) of test and control groups were 38.84± 10.60 and 39.58 ±11.68 respectively. Prevalence of thyroid dysfunction among the study subjects was 36.4% and 7.6% in the controls. Subclinical hypothyroidism was the most common prevalent type of thyroid dysfunction in both test and control groups at 17.6% and 7.2% respectively. In the test group, sick euthyroid syndrome (17.2%) ranked second while in the controls, primary hypothyroidism (7.2%) was the second commonest dysfunction. CONCLUSION: Thyroid dysfunction was more common in HAART-naïve HIV sero-positive subjects than in the general population with subclinical hypothyroidism emerging as the commonest abnormality.

CONTEXTE: Le VIH/SIDA est une maladie multisystémique qui a été associée à plusieurs endocrinopathies, dont la thyroïde associée à plusieurs endocrinopathies, y compris le dysfonctionnement de la dysfunctionnement. Le dysfonctionnement thyroïdien chez les patients atteints du VIH/SIDA, entre autres facteurs, peut être due aux effets cytopathiques directs du cytopathiques directs du VIH sur la glande thyroïde, en plus des effets indésirables des médicaments antirétroviraux hautement actifs (HAART). OBJECTIF DE L'ÉTUDE: L'étude visait à déterminer la prévalence et le modèle de dysfonctionnement thyroïdien chez les patients VIH naïfs de traitement HAART à Enugu. MATÉRIEL ET MÉTHODES: L'étude était transversale, basée sur un cas-témoin, impliquant 250 patients séropositifs n'ayant jamais reçu de HAART et 250 patients séronégatifs et 250 sujets séronégatifs. Des mesures anthropométriques et un examen physique ont été effectués. Les dosages de fT3, fT4, TSH (pour la fonction thyroïdienne) a été effectué à l'aide de l'Enzyme Linked Immunoassay (ELISA). Les données ont été analysées en utilisant le progiciel statistiques pour sciences sociales (SPSS) version 23. RÉSULTATS: Les cohortes séropositives n'ayant jamais reçu de HAART comprenaient 112 hommes et 138 femmes, tandis que les sujets témoins comprenaient 125 hommes et 125 femmes. Les âges moyens (années) des groupes test et groupes témoins étaient respectivement de 38,84± 10,60 et 39,58 ±11,68. La prévalence du dysfonctionnement de la thyroïde parmi les sujets de l'étude était de 36,4 % et 7,6 % chez les témoins. L'hypothyroïdie subclinique était le type de dysfonctionnement thyroïdien le plus répandu dans les groupes test et témoin soit 17,6 % et 7,2 % respectivement. Dans le groupe test, le syndrome d'euthyroïdie maladive (17,2 %) arrivait en deuxième position, tandis que dans le groupe témoin, l'hypothyroïdie primaire (7,2 %) était le deuxième type de dysfonctionnement le plus courant. CONCLUSION: Les dysfonctionnements de la thyroïde étaient plus fréquents chez les personnes suivantes sujets séropositifs n'ayant jamais reçu de traitement antirétroviral que dans la population générale, l'hypothyroïdie subclinique apparaissant comme la l'anomalie la plus fréquente. MOTS-CLÉS: Prévalence, Modèle, HAART-naïf, patients VIH, dysfonctionnement de la thyroïde, Nigéria.

Insulin resistance, metabolic syndrome, and lipids in African women.

BACKGROUND: The metabolic syndrome is closely related to insulin resistance (IR) and cardiovascular disease. This study examined the prevalence of IR and metabolic syndrome as well as factors associated with IR among Nigerian women. MATERIALS AND METHODS: Eighty-six women living in an urban area in Enugu, South-East Nigeria, were assessed. Demographic information included age, residence, physical activity, alcohol and tobacco intake and were collected with questionnaires. Blood pressure and anthropometric parameters were measured using standard methods. Fasting lipids, blood glucose, and insulin were measured. IR was calculated with homeostasis model assessment of IR formula. The ratios; triglyceride/high-density lipoprotein (TG/HDL), total cholesterol (TC)/HDL, and atherogenic index of plasma; log (TG/HDL) were calculated and compared with IR. Metabolic syndrome was sought for using both the WHO and the harmonized joint criteria. RESULTS: The mean age was 44.4 (13.1) years. Hypertension, obesity/overweight, and abdominal obesity were present in 31.5%, 81.1%, and 92.2%, respectively. There was elevated TC (62.2%), elevated low-density lipoprotein (45.6%), low HDL (40%), and elevated TG (14.4%) levels. IR was present in 39 (45.3%). Metabolic syndrome was present in 25 (29.1%) and 17 (19.8%) using the joint criteria and the WHO criteria, respectively. The sensitivity and specificity of the joint revised criteria in identifying IR individuals were 48.7% and 87.2%, respectively, and for the WHO criteria, were 38.5% and 95.7%, respectively. The only significant predictor of IR was the presence of diabetes; P = 0.03, odds ratio = 7.2 (95% confidence interval = 1.19-41.88). CONCLUSION: IR and metabolic syndrome were common. They were not related to any of the lipoprotein ratios. Metabolic syndrome had a low sensitivity in detecting IR.

Systems genetic and pharmacological analysis identifies candidate genes underlying mechanosensation in the von Frey test.

Mechanical sensitivity is commonly affected in chronic pain and other neurological disorders. To discover mechanisms of individual differences in punctate mechanosensation, we performed quantitative trait locus (QTL) mapping of the response to von Frey monofilament stimulation in BXD recombinant inbred (BXD) mice. Significant loci were detected on mouse chromosome (Chr) 5 and 15, indicating the location of underlying polymorphisms that cause heritable variation in von Frey response. Convergent evidence from public gene expression data implicates candidate genes within the loci: von Frey thresholds were strongly correlated with baseline expression of Cacna2d1, Ift27 and Csnk1e in multiple brain regions of BXD strains. Systemic gabapentin and PF-670462, which target the protein products of Cacna2d1 and Csnk1e, respectively, significantly increased von Frey thresholds in a genotype-dependent manner in progenitors and BXD strains. Real-time polymerase chain reaction confirmed differential expression of Cacna2d1 and Csnk1e in multiple brain regions in progenitors and showed differential expression of Cacna2d1 and Csnk1e in the dorsal root ganglia of the progenitors and BXD strains grouped by QTL genotype. Thus, linkage mapping, transcript covariance and pharmacological testing suggest that genetic variation affecting Cacna2d1 and Csnk1e may contribute to individual differences in von Frey filament response. This study implicates Cacna2d1 and Ift27 in basal mechanosensation in line with their previously suspected role in mechanical hypersensitivity. Csnk1e is implicated for von Frey response for the first time. Further investigation is warranted to identify the specific polymorphisms involved and assess the relevance of these findings to clinical conditions of disturbed mechanosensation.

Social disruption alters pain and cognition in an animal model of multiple sclerosis.

Although pain and cognitive deficits are widespread and debilitating symptoms of multiple sclerosis (MS), they remain poorly understood. Theiler's murine encephalomyelitis virus (TMEV) infection is an animal model of MS where disease course is exacerbated by prior stressors. Here chronic infection coupled with prior social stress increased pain behavior and impaired hippocampal-dependent memory consolidation during the demyelinating phase of disease in SJL mice. These results suggest that the TMEV model may be useful in investigating pain and cognitive impairments in MS. However, in contrast to prior Balb/cJ studies, stress failed to consistently alter behavioral and physiological indicators of disease course.

Social disruption induced priming of CNS inflammatory response to Theiler's virus is dependent upon stress induced IL-6 release.

Chronic social disruption stress (SDR) exacerbates acute and chronic phase Theiler's murine encephalomyelitis virus (TMEV) infection, a mouse model of multiple sclerosis. However, the precise mechanism by which this occurs remains unknown. The present study suggests that SDR exacerbates TMEV disease course by priming virus-induced neuroinflammation. It was demonstrated that IL-1ß mRNA expression increases following acute SDR; however, IL-6 mRNA expression, but not IL-1ß, is upregulated in response to chronic SDR. Furthermore, this study demonstrated SDR prior to infection increases infection related central IL-6 and IL-1ß mRNA expression, and administration of IL-6 neutralizing antibody during SDR reverses this increase in neuroinflammation.

Endocrine and metabolic disorders associated with human immune deficiency virus infection.

BACKGROUND: Many reports have described endocrine and metabolic disorders in the human immunodeficiency virus (HIV) infection. This article reviewed various reports in the literature in order to increase the awareness and thus the need for early intervention when necessary. DATA SOURCE: Data were obtained from MEDLINE, Google search and otherjournals on 'HIV, Endocrinopathies/Metabolic Disorders' from 1985 till 2007. STUDY SELECTION: Studies related to HIV associated endocrinopathies and metabolic disorders in the last two decades were reviewed. DATA EXTRACTION: Information on epidemiology, pathogenesis, diagnosis and treatment of the target organ endocrinopathies and metabolic disorders in HIV/AIDS were extracted from relevant literature. RESULTS: Endocrine and metabolic disturbances occur in the course of HIV infection. Pathogenesis includes direct infection of endocrine glands by HIV or opportunistic organisms, infiltration by neoplasms and side effects of drugs. Adrenal insufficiency is the commonest HIV endocrinopathy with cytomegalovirus adrenalitis occurring in 40-88% of cases. Thyroid dysfunction may occur as euthyroid sick syndrome or sub-clinical hypothyroidism. Hypogonadotrophic dysfunction accounts for 75% of HIV-associated hypogonadism, with prolonged amenorrhoea being three times more likely in the women. Pancreatic dysfunction may result in hypoglycaemia or diabetes mellitus (DM). Highly active antiretroviral therapy (HAART) especially protease inhibitors has been noted to result in insulin resistance and lipodystrophy. CONCLUSION: Virtually every endocrine organ is involved in the course of HIV infection. Detailed endocrinological and metabolic evaluation and appropriate treatment is necessary in the optimal management of patients with HIV infection in our environment.

Chicken Mhc alloantiserum cross-reactivity analysis by hemagglutination and flow cytometry.

The major histocompatibility complex (Mhc) haplotype in the chicken is generally determined by the use of alloantisera in a hemagglutination assay. This method restricts haplotype determination to antigens expressed on the surface of erythrocytes which includes class I (B - F) and class IV (B - G) antigens as well as any other polymorphic molecules on these cells. Alloantisera can result in complex cross-reactivity patterns. We describe here the analysis of 53 alloantisera made within Mhc-congenic lines. Each antiserum was tested by hemagglutination with erythrocytes and by flow cytometry with erythrocytes and peripheral white blood cells of seven Mhc haplotypes; B2, B5, B12, B13, B15, B19 , and B21 . Five types of antiserum were identified based on their reactivity to different cell subpopulations of the peripheral blood of the donor haplotype as well as in cross-reactivity for different haplotypes. RBC specific cross-reactive antigens attributed to B - G molecules were demonstrated for the B5 : B19, B12 : B19, and B19 : B21 cross-reactions. Cross-reactive antigens detected on RBC and thrombocytes attributable to B - G molecules on both types of cells were demonstrated for the B2 : B12, B2 : B15, B2 : B19, and B2 : B21 cross-reactions. In addition, cross-reactive antigens occurring on RBC and WBC were attributed to B - F (or RBC and lymphocyte-expressed B - G loci) and included the B12 : B13, B13 : B19, and B15 : B19 cross-reactions. Several antisera with specificity for B cells purportedly identifying B - L epitopes were found but their numbers were limited and cross-reactivities were not defined. The identities described here may be useful in understanding B haplotype similarities and differences in disease resistance and immune response.

Coordinate regulation of the four tubulin genes of Chlamydomonas reinhardi.

During cell division and during the induction of tubulin synthesis that accompanies flagellar regeneration in Chlamydomonas reinhardi, four tubulin mRNAs of discrete molecular sizes are produced. During induction two beta tubulin mRNAs (2.47 kb and 2.34 kb) and two alpha tubulin mRNAs (2.26 kb and 2.13 kb) are synthesized in high abundance and in a closely coordinated fashion. Combined data from restriction enzyme mapping (i.e., Southern analysis) of genomic DNA and of Charon 30 recombinant clones bearing inserts of Chlamydomonas tubulin genes provide direct evidence for four distinct tubulin genes in this organism. Dot-blot analysis of the level of hybridization of a 32p nick-translated beta tubulin cDNA to genomic DNA from gametic cells and to a clone containing the beta 1 tubulin gene indicate that each beta 1 tubulin gene is present in one copy per cell. Additional hybridization experiments employing fragments of cDNA clones which selectively anneal to either the 3' or 5' portions of the two alpha tubulin genes or to one or both of the two beta tubulin genes suggest that each tubulin gene is actively transcribed to give rise to one of the four tubulin mRNAs. These observations further suggest that at most four basic types of tubulin subunits are produced by Chlamydomonas and that the heterogeneity of tubulin subunits reported to exist in the flagellar axoneme must arise as a result of post-translational modification.

Tubulin induction in C. reinhardii: requirement for tubulin mRNA synthesis.

Flagellar excision in Chlamydomonas reinhardii triggers a rapid and extensive induction of tubulin synthesis. Cloned plasmids, pFT beta 1 and pFT beta 2, carrying cDNA inserts complementary to beta-tubulin mRNA, have been prepared and used to demonstrate a direct requirement for tubulin mRNA synthesis during tubulin induction. Increased tubulin mRNA synthesis is detected within 5 min after deflagellation. During the 45 min peak period of tubulin synthesis, tubulin mRNA accumulates to levels 15- to 35-fold higher than those found in control (non-deflagellated) cells. In addition, there appears to be a direct correlation between tubulin mRNA concentrations and the levels of tubulin production during the induction and deinduction cycle that accompanies flagellar regeneration. Amiprophosmethyl (APM), a compound we reported earlier as a selective inhibitor of tubulin synthesis in deflagellated cells, is shown to block the accumulation of tubulin mRNA following flagellar excision and to cause the rapid loss of tubulin mRNA from cells treated at the peak of induction.

Calcium dependence of phalloidin-induced liver cell death.

The role of Ca2+ in toxic liver cell death was studied with primary cultures of adult rat hepatocytes. Within 1 hr of exposure to phalloidin, a bicyclic heptapeptide isolated from the mushroom Amanita pahlloides, at 50 micrograms/ml, 60--70% of the cells were dead (trypan blue stainable). There was no loss of viability of the same cells exposed to phalloidin in culture medium devoid of Ca2+. A marked structural alteration of the surface of the phalloidin-treated hepatocytes characterized by innumerable evaginations seen by scanning electron microscopy occurred in the presence or absence of Ca2+. Pretreatment of the cells with cytochalasin B at 10 micrograms/ml prevented the surface alteration and the death of the cells in Ca2+ medium. Exposure of the cells to phalloidin in the absence of Ca2+ followed by exposure to cytochalasin B and then to Ca2+ also prevented the cell death. These results suggest a two-step mechanism by which phalloidin causes liver cell death. Initially phalloidin interacts in a Ca2+-independent process with cell membrane-associated actin. The second step is a Ca2+-dependent process that most likely represents an increased influx of Ca2+ across a compromised cell membrane permeability barrier and down the steep concentration gradient that exists between the outside and inside of the cell. These results strengthen the hypothesis that disturbances in Ca2+ homeostasis induced in vivo by a variety of hepatotoxins are causally related to liver cell death.

Calcium dependence of toxic cell death: a final common pathway.

Primary cultures of adult rat hepatocytes were treated in the presence or absence of extracellular calcium with ten different membrane-active toxins. In all cases more than half the cells were killed in 1 to 6 hours in the presence but not in the absence of extracellular calcium. An effect of calcium on the primary mechanism of membrane injury by any of the agents cannot be implicated. Viability, as determined by trypan blue exclusion correlated well with other indices of viability such as plating efficiency and the hydrolysis of fluorescein diacetate. It is concluded that the cells are killed by processes that involve at least two steps. In each type of injury, disruption of the integrity of the plasma membrane by widely differing mechanisms is followed by a common functional consequence involving extracellular calcium, and most likely representing an influx of calcium across the damaged plasma membrane and down a steep concentration gradient. This later step represents, or at least initiates, a final common pathway for the toxic death of these cells.