Neuroprotective role of vitamin D3 in colchicine-induced Alzheimer’s disease in rats

Background: Alzheimer’s disease (AD) is a complex neurodegenerative disease characterized by progressive decline in memory, language and other cognitive functions. Recent studies provide convincing evidence on the role of vitamin D3 on the nervous system.Aim: To investigate the effect of the active form of vitamin D3 (1,25-dihydroxycholecalciferol) as a neuroprotective agent in experimentally induced AD in rats.Methods: 40 adult male Wistar (albino) rats weighing 180 to 200 g were included in this study. Rats were divided into four groups (each of 10 rats): Group I: normal healthy rats receiving intracerebroventricular injection (icv) of artificial cerebrospinal fluid (ACSF) and serving as a control group. Group II: rats with induced AD by icv colchicine injection of 15 lg/rat bilaterally and receiving no treatment. Group III: rats pre-treated with active form of vitamin D3 42 IU/kg/day subcutaneously (s.c.) for one week followed by induction of AD then post-treated with vitamin D3 in the same dose for 3 weeks. Group IV: rats with induced AD then post-treated with vitamin D3 for 3 weeks. The following parameters were evaluated in rats of all studied groups1- Behavioral assessment: Morris water maze and open field tasks were performed at days   13, 14 and 21 post-icv injection for assessing cognitive, gross behavioral and motor activities of studied groups.2- Biochemical tests: Hippocampal tissue levels of brain derived neurotrophic factor (BDNF), amyloid beta (Ab) peptide, and antioxidant system; glutathione reductase (GR) and glutathione peroxidase (GPX).Results: The present study revealed a significant increase in time latency of water maze test and hippocampal tissue level of Ab peptide concomitant with significant reduction of hippocampal tissue levels of BDNF, GR and GPX, in untreated AD rats (group II) versus control ACSF-injected rats (group I) and vitamin D3-treated AD rats (groups III and IV). However, group III (AD rats pre- and post-treated with vitamin D3) showed a significant decrease in time latency and Ab peptide, and a significant elevation of BDNF, GR and GPX, versus group IV (AD rats post-treated with vitamin D3).Conclusion: Prophylactic use of active form of vitamin D3 (1,25(OH)2D3) appears to possess a neuroprotective effect in AD involving various mechanisms. Hence, vitamin D3 or its analogues can be considered as promising agents for development of new prophylactic and therapeutic neuroprotectors

Hyperthyroidism as a reversible cause of right ventricular overload and congestive heart failure

We describe a case of severe congestive heart failure and right ventricular overload associated with overt hyperthyroidism, completely reversed with antithyroid therapy in a few week. It represents a very unusual presentation of overt hyperthyroidism because of the severity of right heart failure. The impressive right ventricular volume overload made mandatory to perform transesophageal echo and angio-TC examination to exclude the coexistence of ASD or anomalous pulmonary venous return. Only a few cases of reversible right heart failure, with or without pulmonary hypertension, have been reported worldwide. In our case the most striking feature has been the normalization of the cardiovascular findings after six weeks of tiamazole therapy

Reversible Pulmonary Hypertension and Isolated Right-sided Heart Failure Associated with Hyperthyroidism

Hyperthyroidism may present with signs and symptoms related to dysfunction of a variety of organs. Cardiovascular pathology in hyperthyroidism is common. A few case reports describe isolated right heart failure, tricuspid regurgitation, and pulmonary hypertension as the prominent cardiovascular manifestations of hyperthyroidism. Although most textbooks do not mention hyperthyroidism as a cause of pulmonary hypertension and isolated right heart failure, the literature suggests that some hyperthyroid patients may develop reversible pulmonary hypertension and isolated right heart failure. We report a case of hyperthyroidism presenting with signs and symptoms of isolated right heart failure, tricuspid regurgitation, and pulmonary hypertension, which resolved with treatment of hyperthyroidism

Birth defects in newborns and stillborns: an example of the Brazilian reality

<p>Abstract</p> <p>Background</p> <p>This study constitutes a clinical and genetic study of all newborn and stillborn infants with birth defects seen in a period of one year in a medical school hospital located in Brazil. The aims of this study were to estimate the incidence, causes and consequences of the defects.</p> <p>Methods</p> <p>For all infants we carried out physical assessment, photographic records, analysis of medical records and collection of additional information with the family, besides the karyotypic analysis or molecular tests in indicated cases.</p> <p>Result</p> <p>The incidence of birth defects was 2.8%. Among them, the etiology was identified in 73.6% (ci95%: 64.4-81.6%). Etiology involving the participation of genetic factors single or associated with environmental factors) was more frequent 94.5%, ci95%: 88.5-98.0%) than those caused exclusively by environmental factors (alcohol in and gestational diabetes mellitus). The conclusive or presumed diagnosis was possible in 85% of the cases. Among them, the isolated congenital heart disease (9.5%) and Down syndrome (9.5%) were the most common, followed by gastroschisis (8.4%), neural tube defects (7.4%) and clubfoot (5.3%). Maternal age, parental consanguinity, exposure to teratogenic agents and family susceptibility were some of the identified risk factors. The most common observed consequences were prolonged hospital stays and death.</p> <p>Conclusions</p> <p>The current incidence of birth defects among newborns and stillbirths of in our population is similar to those obtained by other studies performed in Brazil and in other underdeveloped countries. Birth defects are one of the major causes leading to lost years of potential life. The study of birth defects in underdeveloped countries should continue. The identification of incidence, risk factors and consequences are essential for planning preventive measures and effective treatments.</p

The concept of "compartment allergy": prilocaine injected into different skin layers

We herein present a patient with delayed-type allergic hypersensitivity against prilocaine leading to spreading eczematous dermatitis after subcutaneous injections for local anesthesia with prilocaine. Prilocaine allergy was proven by positive skin testing and subcutaneous provocation, whereas the evaluation of other local anesthetics - among them lidocaine, articaine and mepivacaine - did not exhibit any evidence for cross-reactivity

Applicability of T1-weighted MRI in the assessment of forensic age based on the epiphyseal closure of the humeral head

This work investigates the value of magnetic resonance imaging analysis of proximal epiphyseal fusion in research examining the growth and development of the humerus and its potential utility in establishing forensic age estimation. In this study, 428 proximal humeral epiphyses (patient age, 12-30years) were evaluated with T1-weighted turbo spin echo (T1 TSE) sequences in coronal oblique orientation on shoulder MRI images. A scoring system was created following a combination of the Schmeling and Kellinghaus methods. Spearman's rank correlation analysis revealed a significant positive relationship between age and ossification stage of the proximal humeral epiphysis (all subjects: rho=0.664, p<0.001; males: 0.631, p<0.001; females: rho=0.651, p<0.001). The intra- and inter-observer reliability assessed using Cohen's kappa statistic was =0.898 and =0.828, respectively. The earliest age of epiphysis closure was 17years for females and 18years for males. MRI of the proximal humeral epiphysis can be considered advantageous for forensic age estimation of living individuals in a variety of situations, ranging from monitoring public health to estimating the age of illegal immigrants/asylum seekers, minors engaged in criminal activities, and illegal participants in competitive sports, without the danger of radiation exposure

Identification of Prognostic Molecular Features in the Reactive Stroma of Human Breast and Prostate Cancer

Primary tumor growth induces host tissue responses that are believed to support and promote tumor progression. Identification of the molecular characteristics of the tumor microenvironment and elucidation of its crosstalk with tumor cells may therefore be crucial for improving our understanding of the processes implicated in cancer progression, identifying potential therapeutic targets, and uncovering stromal gene expression signatures that may predict clinical outcome. A key issue to resolve, therefore, is whether the stromal response to tumor growth is largely a generic phenomenon, irrespective of the tumor type or whether the response reflects tumor-specific properties. To address similarity or distinction of stromal gene expression changes during cancer progression, oligonucleotide-based Affymetrix microarray technology was used to compare the transcriptomes of laser-microdissected stromal cells derived from invasive human breast and prostate carcinoma. Invasive breast and prostate cancer-associated stroma was observed to display distinct transcriptomes, with a limited number of shared genes. Interestingly, both breast and prostate tumor-specific dysregulated stromal genes were observed to cluster breast and prostate cancer patients, respectively, into two distinct groups with statistically different clinical outcomes. By contrast, a gene signature that was common to the reactive stroma of both tumor types did not have survival predictive value. Univariate Cox analysis identified genes whose expression level was most strongly associated with patient survival. Taken together, these observations suggest that the tumor microenvironment displays distinct features according to the tumor type that provides survival-predictive value

Th1-Th17 Cells Mediate Protective Adaptive Immunity against Staphylococcus aureus and Candida albicans Infection in Mice

We sought to define protective mechanisms of immunity to Staphylococcus aureus and Candida albicans bloodstream infections in mice immunized with the recombinant N-terminus of Als3p (rAls3p-N) vaccine plus aluminum hydroxide (Al(OH3) adjuvant, or adjuvant controls. Deficiency of IFN-γ but not IL-17A enhanced susceptibility of control mice to both infections. However, vaccine-induced protective immunity against both infections required CD4+ T-cell-derived IFN-γ and IL-17A, and functional phagocytic effectors. Vaccination primed Th1, Th17, and Th1/17 lymphocytes, which produced pro-inflammatory cytokines that enhanced phagocytic killing of both organisms. Vaccinated, infected mice had increased IFN-γ, IL-17, and KC, increased neutrophil influx, and decreased organism burden in tissues. In summary, rAls3p-N vaccination induced a Th1/Th17 response, resulting in recruitment and activation of phagocytes at sites of infection, and more effective clearance of S. aureus and C. albicans from tissues. Thus, vaccine-mediated adaptive immunity can protect against both infections by targeting microbes for destruction by innate effectors