Concomitant dysregulation of androgen secretion and dysfunction of adipose tissue induced insulin resistance

Hyperandrogenism and hyperinsulinemia have resulted from dysfunction of the theca cell of the ovary and adipose tissue and each one potentiates the other in patients with androgen excess disorders e.g., polycystic ovary disease and idiopathic hirsutism. Possible external and/or internal triggers can produce such cellular dysfunction. There is evidence that sodium valproate acts as a trigger of cellular dysfunction and produces both hyperinsulinemia and hyperandrogenism. Therefore, the elimination of these triggers can help the patients to recover from hyperinsulinemia, insulin resistance and hyperandrogenism.     

Afferent responses during experimentally induced semicircular canalithiasis

Benign paroxysmal positional vertigo (BPPV) is a common vestibular disorder that results in brief periods of vertigo and nystagmus, when the head is tipped relative to gravity. Symptoms are commonly attributed to the pathological presence of heavy calcium carbonate particles within the lumen of the semicircular canal(s)-a condition termed canalithiasis. In the present work, we induced canalithiasis in an animal model (oyster toadfish, Opsanus tau) by introducing heavy glass microbeads into the lumen of the lateral semicircular canal. Bead movement under the action of gravity and canal afferent nerve discharge were recorded in vivo. When the head was oriented nose-down, beads moved toward the nose and the lateral canal afferent discharge rate increased. Afferents that normally encoded angular velocity during oscillatory head rotations responded with tonic increases in the discharge rate during gravity-dependent bead movement. Other afferents, such as the units that rapidly adapt to a step increase in angular head velocity, responded with an initial increase in discharge rate followed by a period of adaptation. Afferent responses occurred in the complete absence of head movement and quantify the pathological inputs to the brain that arise from canalithiasis. The magnitude and time course of the responses reported here are sufficient to explain the symptoms of BPPV.     

Successful renal transplantation in a family with a novel mutation in COL4A3 gene and autosomal recessive Alport syndrome

Alport syndrome (AS) is an inherited disorder of basement membranes caused by mutations affecting specific proteins of the type IV collagen family, presenting with nephropathy and extrarenal manifestations such as sensorineural deafness and ocular anomalies. Ten percentage to 15% of the patients with AS have autosomal recessive (ARAS) due to mutation in either COL4A3 or COL4A4 gene. We report a novel mutation in the COL4A3 gene in an Indian family with ARAS. The above‐mentioned genetic anomaly was a missense variation in exon 26 of the COL4A3 gene (chr2:228137797G>A; c.1891G>A) that resulted in the amino acid substitution of Arginine for Glycine at codon 631 (p.Gly631Arg) that was present in the heterozygous state in the asymptomatic parents and homozygous state in the male offspring who presented with early‐onset end‐stage renal disease, lenticonus and hearing loss. The patient (male offspring) underwent successful renal transplantation with his mother as a donor.     

Analysis of platelet adhesion to a collagen-coated surface under flow conditions: the involvement of glycoprotein VI in the platelet adhesion

Platelet adhesion to the exposed surface of the extracellular matrix in flowing blood is the first and critical reaction for in vivo thrombus formation. However, the mechanism of this in vivo platelet adhesion has yet to be studied extensively. One of the reasons for this is the lack of a practical assay method for assessing platelet adhesion under flow conditions. We have devised an assay method (the fluorescent adhesion assay) that is based on the technique originally reported by Hubbell and McIntire (Biomaterials 7:354, 1986) with some modifications to make it more amenable for assaying small samples and have developed an analysis method to quantify the extent of platelet adhesion and aggregation from fluorescence images by using a computer-assisted image analysis system. In our assay, platelet adhesion, expressed as the percentage of the area covered by adhered platelets, was found to increase biphasically as a function of time. In the first phase, platelets interacted with the coated collagen, transiently stopping on the surface; we called this reaction the temporary arrest. In the second phase, platelets adhered much more rapidly and permanently on the surface, and this adhesion was dependent on the shear rate; platelets formed aggregates in this phase. We used our assay to analyze the effects of platelet aggregation inhibitors on platelet adhesion. All three examined inhibitors, EDTA (10 mmol/L), antiglycoprotein (GP) IIb/IIIa, and GRGDS peptide (1 mmol/L), inhibited the second phase adhesion in flowing blood. Furthermore, GPVI-deficient platelets also showed defective second-phase adhesion under the same conditions. These results suggested that GPIIb/IIIa activation and GPVI contribute to the reaction inducing the second phase. The second-phase adhesion has been extensively investigated, and the consensus is that this reaction is mainly attributable to the platelet-platelet interaction. In this report, we were able to detect an earlier reaction, the temporary arrest. This temporary arrest would reflect the fast and weak interaction between platelet GPIb/IX and collagen-von Willebrand factor complexes on the collagen-coated surface.