Peripheral mechanical loading and the mechanism of the tremor of chronic alcoholism.

The tremor of chronic alcoholism, although clinically similar to essential tremor, has been considered a distinct syndrome. Its underlying mechanism was analyzed in five patients (none in the acute stages of alcohol withdrawal) hospitalized in an alcohol detoxification program. All five patients performed tracking tasks in which they pursued a linearly moving "target" light with a response light that they controlled by flexion-extension activity of the wrist. Stationary and dynamic targets were used with both isometric and unconstrained wrist mechanical interfaces. Frequency, torque, and displacement tremor characteristics were examined under varying inertial loading or isometric voluntary torque conditions. Two simultaneous tremor components were present in all patients: a prominent 4- to 7-Hz low-frequency peak and a smaller-amplitude 9.4- to 9.6-Hz high-frequency peak. As the inertia of the hand was augmented during unconstrained tasks, the low-frequency peak decreased, while the high-frequency peak was unaffected. As required voluntary effort was increased during isometric testing, the amplitude of the low-frequency peak increased. These findings suggest that the low-frequency peak represents the significant pathologic component of the tremor of chronic alcoholism and that it has a biomechanical reflex mechanism similar to that of the lower-amplitude normal physiologic tremor.     

The SLC26 gene family of multifunctional anion exchangers

The ten-member SLC26 gene family encodes anion exchangers capable of transporting a wide variety of monovalent and divalent anions. The physiological role(s) of individual paralogs is evidently due to variation in both anion specificity and expression pattern. Three members of the gene family are involved in genetic disease; SLC26A2 in chondrodysplasias, SLC26A3 in chloride-losing diarrhea, and SLC26A4 in Pendred syndrome and hereditary deafness (DFNB4). The analysis of Slc26a4-null mice has significantly enhanced the understanding of the roles of this gene in both health and disease. Targeted deletion of Slc26a5 has in turn revealed that this paralog is essential for electromotor activity of cochlear outer hair cells and thus for cochlear amplification. Anions transported by the SLC26 family, with variable specificity, include the chloride, sulfate, bicarbonate, formate, oxalate and hydroxyl ions. The functional versatility of SLC26A6 identifies it as the primary candidate for the apical Cl(-)-formate/oxalate and Cl(-)-base exchanger of brush border membranes in the renal proximal tubule, with a central role in the reabsorption of Na(+)-Cl(-) from the glomerular ultrafiltrate. At least three of the SLC26 exchangers mediate electrogenic Cl(-)-HCO(3)(-) and Cl(-)-OH(-) exchange; the stoichiometry of Cl(-)-HCO(3)(-) exchange appears to differ between SLC26 paralogs, such that SLC26A3 transports >/=2 Cl(-) ions per HCO(3)(-) ion, whereas SLC26A6 transports >/=2 HCO(3)(-) ions per Cl(-) ion. SLC26 Cl(-)-HCO(3)(-) and Cl(-)-OH(-) exchange is activated by the cystic fibrosis transmembrane regulator (CFTR), implicating defective regulation of these exchangers in the reduced HCO(3)(-) transport seen in cystic fibrosis and related disorders; CFTR-independent activation of these exchangers is thus an important and novel goal for the future therapy of cystic fibrosis.     

Prosthetic mitral valve endocarditis due to Ochrobactrum anthropi: case report

We describe a case of infective endocarditis in a prosthetic mitral valve due to Ochrobactrum anthropi. Although O. anthropi is an emerging pathogen in immunocompromised patients, infections with the bacterium have very rarely been documented in healthy hosts, and endocarditis is rare. To our knowledge, only two cases of O. anthropi endocarditis have been reported in the medical literature.     

Distinct Leishmania braziliensis isolates induce different paces of chemokine expression patterns

Inflammatory events during Leishmania braziliensis infection in mice were investigated. Large lesions were directly correlated with the inflammatory reaction but not with parasite burden. Different L. braziliensis strains induce different paces of chemokine expression patterns, leading to diverse cell recruitment and differential inflammatory responses.     

Pregnancies after intracytoplasmic sperm injection with cryopreserved testicular spermatozoa

In 25 patients (14 suffering from obstructive azoospermia, sixfrom non-obstructive azoospermia, three from astheno-azoospermiaand two from absence of ejaculation) spermatozoa were extractedfrom testicular biopsies. Intracytoplasmic sperm injection (ICSI)with fresh testicular spermatozoa was performed in 18 cases;spermatozoa in excess were cryopreserved in pills. No pregnancieswere achieved. In the remaining seven patients, testicular spermatozoawere retrieved and cryopreserved during a diagnostic testicularbiopsy. After thawing, sperm motility was assessed in 17 cases(68%), and 18 ICSI with cryopreserved testicular spermatozoawere performed. The mean two-pronuclear (2PN) fertilizationrate was 59%, the mean cleavage rate was 92%, and six clinicalpregnancies were achieved, all of them still ongoing (pregnancyrate 33%). A comparison of the results of ICSI carried out withfresh or cryopreserved testicular spermatozoa showed that themean 2PN fertilization rates per cycle (53 compared with 55%),mean cleavage rates per cycle (99 compared with 96%) and embryoquality were not significantly different In conclusion, cryopreservationof testicular spermatozoa is feasible, even in patients withnon-obstructive azoospermia, and the results of ICSI with frozen-thawedtesticular spermatozoa are similar to those obtained using freshtesticular spermatozoa. Cryopreservation of testicular spermatozoamay avoid repetition of testicular biopsies to retrieve spermatozoafor successive ICSI cycles in patients in whom the only sourceof motile spermatozoa is the testicle.     

Role of vagal afferents in vasodepressor effects of PGE2 in spontaneously hypertensive rats.

In anesthetized, spontaneously hypertensive rats (Okamoto-Aoki), injections of 0.75, 1.5, and 3.0 microgram/kg PGE2 into the jugular vein caused transient decreases (mean +/- SE) in arterial pressure of 21 +/- 2, 37 +/- 3, and 78 +/- 6 mmHg, respectively, before cervical vagotomy and of 1 +/- 1, 15 +/- 4, and 15 +/- 6 mmHg after cervical vagotomy. The vasodepressor effect of jugular vein injections of 3.0 microgram/kg PGE2, but not of lower doses, was depressed by vagotomy in normotensive Wistar-Kyoto and Sprague-Dawley rats. Vagotomy did not reduce the hypotensive response to intra-aortic injections of PGE2 in these hypertensive and normotensive rats. The depressor effect of PGE2 thus appears to have a significant reflex component mediated through cardiopulmonary receptors subserved by vagal afferents, with hypertensive rats exhibiting a lower threshold than normotensive rats. A vagally mediated reflex component to the depressor effect of PGE2 could not be demonstrated in normotensive rabbits or in rabbits and rats with chronic renovascular hypertension. Thus, a naturally occurring vasoactive substance can stimulate cardiopulmonary receptors subserved by vagal afferents in the rat, and spontaneously hypertensive rats appear to be especially sensitive to this effect.     

Mutational diversity and hot spots in the alpha-sarcoglycan gene in autosomal recessive muscular dystrophy (LGMD2D).

Sarcoglycanopathies are a genetically heterogeneous group of autosomal recessive muscular dystrophies in which the primary defect may reside in any of the genes coding for the different partners of the sarcolemmal sarcoglycan (SG) complex: the alpha-SG (LGMD2D at 17q21.2), the beta-SG (LGMD2E at 4q12), the gamma-SG (LGMD2C at 13q12), and the delta-SG (LGMD2F at 5q33). We report a series of 20 new unrelated families with 14 different mutations in the alpha-SG gene. Along with the mutations that we previously reported this brings our cohort of patients with alpha-sarcoglycanopathy to a total of 31 unrelated patients, carrying 25 different mutations. The missense mutations reside in the extracellular domain of the protein. Five of 15 missense mutations, carried by unrelated subjects on different haplotype backgrounds and of widespread geographical origins, account for 58% of the mutated chromosomes, with a striking prevalence of the R77C substitution (32%). The severity of the disease varies strikingly and correlates at least in part with the amount of residual protein and the type of mutation. The recurrent R284C substitution is associated with a benign disease course.