Colonic Drug Delivery: Enhanced Release of Indomethacin from Cross-Linked Chondroitin Matrix in Rat Cecal Content

Pharmaceutical Research -     

Superior displacement of the hip in total joint replacement: Effects of prosthetic neck length,neck-stem angle,and anteversion angle on the moment-generating capacity of the muscles

The purpose of this study was to determine the effects of superior displacement of the hip center and changes in three prosthetic parameters (neck length, neck-stem angle, and anteversion angle) on the capacity of muscles to generate force and moment about the hip. A three-dimensional model that calculates the maximum isometric forces and moments generated by 25 muscles crossing the hip over a wide range of body positions was used to evaluate the effects of a 2 cm elevation of the hip center and changes in the prosthetic parameters. After superior displacement of the hip center, the neck length was increased from 0 to 3 cm, the neck-stem angle was varied between 110 and 150°, and the anteversion angle was varied between 0 and 40°. Our analysis showed that a 2 cm superior displacement of the hip center would decrease the moment-generating capacity of the four muscle groups studied (abductors, adductors, flexors, and extensors) if neck length were not increased to compensate for decreased muscle length. In the computer model of an adult man that we used, a 2 cm increase in neck length restored the moment-generating capacity of the muscles by increasing muscle length and force-generating capacity. However, a 3 cm increase in neck length increased passive muscle forces substantially, which potentially could limit joint motion. An increased neck-stem angle (i.e., a valgus neck) decreased the abduction moment arm but increased the moment-generating capacity of the other muscle groups. A change in the anteversion angle from 0 to 40° had a relatively small effect on the isometric moment-generating capacity of the muscles studied.     

Comparison of salivary calmodulin binding proteins in Sjögren''s syndrome and healthy individuals

Background: Reduction in salivary secretion is the hallmark of Sjögren's syndrome (SS). Calmodulin (CaM) and calmodulin binding proteins (CaMBPs) play a key role in the secretory process of saliva. Recent studies have suggested that SS‐B, an autoantibody associated with SS, is a CaMBP. This finding suggests that CaMBP may contribute to the loss of saliva in SS. To better understand the role(s) of these proteins in SS, the purpose of this study was to compare salivary CaMBPs in Sjögren's patients and controls. Methods: Saliva samples were collected from 20 patients and 20 age‐, race‐, and gender‐matched controls. CaM overlay was used to identify CaMBPs in saliva of patients and controls. Results: Higher number of salivary CaMBPs was observed among patients than controls. Conclusions: The increased number of salivary CaMBPs in SS may suggest a potential role for these proteins in the pathogenesis of the disease.     

Splenic abscess and peritonitis in a continuous ambulatory peritoneal dialysis (CAPD) patient

A 26-year-old female was on continuous ambulatory peritoneal dialysis (CAPD) because of diabetic end-stage renal failure. She developed an acute peritonitis that relapsed repeatedly despite appropriate antibiotic treatment. Investigations showed the presence of a splenic abscess, and splenectomy and peritoneal cannula removal were required. The patient died of myocardial infarction two weeks postoperatively. This is the first recorded case of peritonitis secondary to splenic abscess in a CAPD patient. Autopsy findings suggest that the abscess developed from infection of a splenic infarct.     

Correlation between the induction of an immediate early gene, zif/268, and long-term potentiation in the dentate gyrus.

Expression of the immediate early gene zif/268 (also termed NGFI-A, Krox 24, TIS8 and Egr-1) was investigated in awake rats following various long-term potentiation (LTP) induction protocols.zif/268 mRNA (Northern blots) and protein (immunohistochemistry) levels sharply increased following LTP, and followed a time course characteristic of other immediate early genes. When measured across 3 tetanization protocols known to produce differing degrees of LTP persistence,zif/268 induction was found to be more highly correlated with LTP duration than with the magnitude of initial LTP. These data support the hypothesis that the immediate early gene zif/268 plays a role as a third messenger in the cascade of cellular and nuclear events that govern the persistence of LTP.     

Decreased platelet vesicular monoamine transporter density in habitual smokers.

The brain vesicular monoamine transporter (VMAT2) is part of the re-uptake mechanism which regulates monoaminergic neurotransmission. We demonstrated previously a high degree of similarity between the pharmacodynamic characteristics of platelet and brain VMAT2. Nicotine induced increase of dopamine and serotonin neurotransmission in limbic structures may alter the expression of VMAT2 in brains of smokers. In this study we measured the VMAT2 pharmacodynamic characteristics using high-affinity [3H]dihydrotetrabenazine (TBZOH) binding to platelets of smokers (n=15) compared to sex and age matched healthy nonsmokers controls (n=14). A significant decrease (17%, P=0.02) in VMAT2 density (Bmax) was observed in platelets of smokers compared to nonsmokers. There was no significant difference in the affinity of [3H]TBZOH to its platelet binding site and the VMAT2 density did not correlate with the heaviness of smoking. The decreased density of the VMAT2 in the platelets of smokers may reflect nicotine induced desensitization of VMAT2, a phenomenon that may be relevant to the addictive properties of nicotine.     

WAIS-R verbal-performance IQ discrepancies in persons with lateralized lesions: utility of a seven subtest short form.

WAIS-R Verbal-Performance IQ difference scores for Ward's (1990) seven subtest short form and the complete WAIS-R were examined in patients with lateralized and diffuse lesions. For both versions, the expected Performance > Verbal pattern was observed in the right hemisphere lesion group, while no summary score differences were seen in the left hemisphere group. Verbal-Performance IQ discrepancies for the short form fell within +/- 5 points of the WAIS-R discrepancy scores in about 75%of the cases, regardless of lesion location. Statistically reliable IQ differences between the complete and abbreviated WAIS-R attained 66%, 91%, and 89% agreement for the left, right, and diffuse groups, respectively. The results support the clinical utility of the seven subtest short form.     

CAG repeat polymorphism within the KCNN3 gene is a significant contributor to susceptibility to anorexia nervosa: a case-control study of female patients and several ethnic groups in the Israeli Jewish population.

The human small-conductance Ca(2+)-activated potassium channel gene KCNN3 has been involved in mechanisms underlying neuronal function and plasticity. A multiallelic CAG repeat polymorphism within the KCNN3 has been associated with schizophrenia and bipolar disorder. We have previously reported in a family-based study that longer CAG repeats are preferentially transmitted to patients with anorexia nervosa (AN). The present study extends the analysis of KCNN3 allele distribution to a larger series of AN female patients and control groups, incorporating information on ethnicity and co-morbidities associated with AN. The data analysis is presented while considering separately the two alleles of each individual, namely a minor (shorter) and a major (longer) allele. This study has found that the KCNN3 allele distribution in the general Israeli population does not differ significantly in at least four Jewish ethnic groups of Ashkenazi, North African, Iraqi, and Yemenite origin. These have been used as control groups in a matched case-control analysis that has demonstrated a significant over-representation of KCNN3 alleles with longer CAG repeats among AN patients (P < 0.001 for the major allele and P = 0.035 for allele sum). Under dichotomization, a significantly higher prevalence of the L allele (>19 repeats) has been observed among AN patients (P < 0.001). While considering AN and co-morbid phenotypes, a tendency towards longer (L) alleles has been observed in the subset of patients with obsessive-compulsive disorder (OCD) co-morbidity. These findings further implicate KCNN3 as a significant contributor to predisposition to AN.     

Mohan's urethral valvotome: a new instrument

Electrothermic fulguration of posterior urethral valves with a resectoscope is difficult in newborns, especially in small for gestation date and premature newborns because of a small caliber urethra. This difficulty has prompted the innovation of the valvotome described. The outer diameter of the valvotome is 3 mm. and it can be easily introduced without stretching the urethra. This instrument has been used successfully in 8 patients to date. Patient age ranged from 3 days to 3 1/2 years with varying degrees of hydronephrosis and hydroureter. All patients have a good urinary stream with regression of the hydronephrosis and hydroureter.     

18F]-Dopa positron emission tomography imaging in early-stage, non-parkin juvenile parkinsonism.

There are few reports of positron emission tomography (PET) in juvenile parkinsonism (JP). We report on the results of (18)F-6-fluoro-L-dopa (FD) PET in a 14-year-old patient with JP of 5 years duration associated with atypical features. This is the youngest subject to be investigated to date. There was a severe asymmetric reduction in striatal FD uptake, with a rostrocaudal gradient in the putamen similar to that seen in adult-onset idiopathic parkinsonism. Extensive DNA analysis in this patient did not show mutations in the parkin gene.