Human chorionic gonadotropin/luteinizing hormone receptor expression in the adult rat spinal cord

The adult and fetal rat brain contains human chorionic gonadotropin/luteinizing hormone (hCG/LH) receptors, that are functional in mediating the neurotropic, neuroendocrine and behavioral actions of gonadotropins. We hypothesized that the spinal cord also contains these receptors. We have now demonstrated by in situ hybridization, immunohistochemistry, and topical autoradiography that the adult rat spinal cord expresses hCG/LH receptors. Positive cells included motoneurons, interneurons and/or glia in the intermediate and ventral gray matter, interneurons and/or glia in the dorsal gray matter, and oligodendrocytes or astrocytes in the white matter. The receptors were able to bind an appropriate ligand, (125)I-hCG. The functional significance of these receptors in the spinal cord is unknown, but we can speculate that they may be neurotrophic in function.     

Chandipura virus: a major cause of acute encephalitis in children in North Telangana, Andhra Pradesh, India

A hospital-based surveillance was undertaken between May 2005 and April 2006 to elucidate the contribution of Chandipura virus (CHPV) to acute viral encephalitis cases in children, seroconversion in recovered cases and to compare the seroprevalences of anti-CHPV IgM and N antibodies in areas reporting cases with those without any case of acute viral encephalitis. During this period, 90 cases of acute encephalitis were hospitalized in the pediatric wards of Mahatma Gandhi Memorial (MGM) Hospital, Warangal. There were 49 deaths (Case Fatality Rate, i.e., CFR of 54.4%). Clinical samples and records were obtained from 52 suspected cases. The cases were below 15 years, majority in 0-4 years (35/52, 67.3%). Computerized tomography (CT) scans and cerebro-spinal fluid (CSF) picture favored viral etiology. No neurological sequelae were observed. CHPV etiology was detected in 25 cases (48.1%, n = 52; RNA in 20, IgM in 3 and N antibody seroconversion in 2). JEV etiology was detected in 5 cases (IgM in 4 cases and seroconversion in 1 case). Anti-CHPV IgM seroprevalence in contacts (26/167, 15.6%) was significantly higher (P < 0.05) than in non-contacts (11/430, 2.6%); which was also observed in children <15 years (19/90, 21.1% vs. 3/109, 2.7%). Anti-CHPV N antibody seroprevalence in <15 years contacts (66/90, 73.3%) and non-contacts (77/109, 70.6%) was significantly lower (P < 0.05) than in contacts (75/77, 97.4%) and non-contacts (302/321, 94.1%) more than 15 years respectively. CHPV appears to be the major cause of acute viral encephalitis in children in endemic areas during early monsoon months.     

Zona pellucida-based contraceptive vaccines for human and animal utility

Contraceptive vaccines can be designed to inhibit (i) production of the gametes (sperm and oocyte), (ii) functions of gametes leading to block in fertilization, and (iii) the gamete outcome (pregnancy). The zona pellucida (ZP) glycoproteins have been proposed as candidates for developing contraceptive vaccines by virtue of their critical role in fertilization. Immunization of non-human primates with either native or recombinant ZP proteins leads to curtailment of fertility, which however is invariably associated with ovarian pathology. To avoid oophoritis, immunogens corresponding to mapped B cell epitopes of ZP proteins that are devoid of 'oophoritogenic' T cell epitopes have been proposed. However, ways to overcome the observed oophoritis associated with the ZP-based contraceptive vaccines are yet to be fully defined. This is essential if their use for control of human fertility is to be considered. Nonetheless, contraceptive vaccines based on ZP proteins have shown very promising results in controlling wildlife population such as wild horses, white-tailed deers, elephants, marsupials, grey seals and dogs, where long term infertility or even permanent sterility is desirable.     

The Role of Microbial Biofilms in Osteonecrosis of the Jaw Associated with Bisphosphonate Therapy

Microbial biofilms have been observed and described in bone specimens of patients with bisphosphonate (BP)-associated osteonecrosis of the jaw (BONJ) and investigators are more recently suggesting that this condition essentially represents an osteomyelitis of the jaw clinically, with greater susceptibility in some patients on BP therapy. This article explains the role of microbial biofilms in BONJ and also discusses associated factors in the disease pathogenesis, which include BP effects on bone remodeling, anti-angiogenesis, matrix necrosis, microcracks, soft tissue toxicity, and inflammation and wound healing. Recent findings suggest a key role for microbial biofilms in the pathogenesis of BONJ; this has important therapeutic implications because biofilm organisms represent a clinical target for prevention and treatment efforts aimed at reducing the significant morbidity and costs associated with this condition.     

Physical and emotional health of mothers of youth with functional abdominal pain

OBJECTIVE: To determine if mothers of youth with functional abdominal pain (FAP) experience more anxiety, depressive, and somatic symptoms and disorders than mothers of unaffected children. DESIGN: Case-control study. SETTING: Four primary care pediatric practices in western Pennsylvania. PARTICIPANTS: Mothers of 8- to 15-year-old children and adolescents presenting with FAP (59 cases) or for routine care in the absence of recurrent pain (76 controls). OUTCOME MEASURES: Questionnaires and blinded interviews assessing anxiety, depressive, and somatic symptoms and disorders; quality of life; and service use. RESULTS: On univariate analyses, mothers of FAP cases were significantly more likely than mothers of controls to have a lifetime history of irritable bowel syndrome (odds ratio [OR], 3.9; 95% confidence interval [CI], 1.5-10.3), migraine (OR, 2.4; 95% CI, 1.1-5.3), and anxiety (OR, 4.8; 95% CI, 2.2-10.6), depressive (OR, 4.9; 95% CI, 2.2-11.0), and somatoform (OR, 16.1; 95% CI, 2.0-129.8) disorders than mothers of controls, and current anxiety, depressive, and somatic symptoms, poorer overall quality of life, and greater use of ambulatory health, but not mental health, services. Multivariate logistic regression found pediatric FAP to be most closely associated with maternal history of anxiety and depression (adjusted OR, 6.1; 95% CI, 1.8-20.8). CONCLUSIONS: Functional abdominal pain may be better conceptualized as a disorder of emotion than a narrowly defined disorder of gastrointestinal function. Low rates of mental health service use by mothers of youth with FAP suggest that family health and illness attitudes deserve study.     

Synaptic competition in the lateral amygdala and the stimulus specificity of conditioned fear: a biophysical modeling study

Competitive synaptic interactions between principal neurons (PNs) with differing intrinsic excitability were recently shown to determine which dorsal lateral amygdala (LAd) neurons are recruited into a fear memory trace. Here, we explored the contribution of these competitive interactions in determining the stimulus specificity of conditioned fear associations. To this end, we used a realistic biophysical computational model of LAd that included multi-compartment conductance-based models of 800 PNs and 200 interneurons. To reproduce the continuum of spike frequency adaptation displayed by PNs, the model included three subtypes of PNs with high, intermediate, and low spike frequency adaptation. In addition, the model network integrated spatially differentiated patterns of excitatory and inhibitory connections within LA, dopaminergic and noradrenergic inputs, extrinsic thalamic and cortical tone afferents to simulate conditioned stimuli as well as shock inputs for the unconditioned stimulus. Last, glutamatergic synapses in the model could undergo activity-dependent plasticity. Our results suggest that plasticity at both excitatory (PN–PN) and di-synaptic inhibitory (PN–ITN and, particularly, ITN–PN) connections are major determinants of the synaptic competition governing the assignment of PNs to the memory trace. The model also revealed that training-induced potentiation of PN–PN synapses promotes, whereas that of ITN–PN synapses opposes, stimulus generalization. Indeed, suppressing plasticity of PN–PN synapses increased, whereas preventing plasticity of interneuronal synapses decreased the CS specificity of PN recruitment. Overall, our results indicate that the plasticity configuration imprinted in the network by synaptic competition ensures memory specificity. Given that anxiety disorders are characterized by tendency to generalize learned fear to safe stimuli or situations, understanding how plasticity of intrinsic LAd synapses regulates the specificity of learned fear is an important challenge for future experimental studies.     

Identification of a novel 45 repeat unstable allele associated with a disease phenotype at the MJD1/SCA3 locus.

We report a three generation Indian pedigree with the proband having 45 repeats at the Machado Joseph Disease (MJD)/spinocerebellar ataxia 3 (SCA3) disease locus. The proband exhibited clinical features of SCA and showed signs of cerebellar and brainstem atrophy on the MRI scan. The 45 repeat allele was unstable upon inter-generational transmission and was associated with a haplotype found in the majority of MJD/SCA3 patients from around the world. This is the smallest unstable allele reported till date at the MJD/SCA3 locus and may greatly reduce the gap between normal and pathological repeat ranges. This article contains supplementary material, which may be viewed at the American Journal of Medical Genetics website at http://www.interscience.wiley.com/jpages/0148-7299:1/suppmat/index.html.