Genetic susceptibility to type 2 diabetic nephropathy in human and animal models

SUMMARY:   Diabetic nephropathy is the most common cause of end-stage renal disease (ESRD) in Japan, Western Europe, and the United States. Mega studies such as Diabetes Control and Complication Trial (DCCT), Epidemiology of Diabetes Interventions and Complications (EDIC), and the United Kingdom Prospective Diabetes Study (UKPDS) clarified that poor glycemic and blood pressure control are undoubtedly involved in the development of nephropathy. However, these factors are not sufficient to predict which diabetic patients will develop renal disease, because not all patients with poor glycemic and blood pressure control develop renal disease. Since ethnic variations and familial clustering of diabetic nephropathy have been observed, genetic factors might contribute to susceptibility to this disease. Several methods such as (genome wide) association studies, sib-pair analysis, and quantitative trait loci (QTLs) analysis are available to examine polygenic diseases. However, no mutations that could explain the majority of nephropathy cases have been identified so far. The development of most diabetic nephropathy might be explained by the polygenic effect (i.e. many minor gene-gene interactions might be very important in the development of nephropathy). Identification of candidate genes of nephropathy enables targeting of therapy in patients at risk and development of novel therapeutic agents.     

Accelerated influx of dendritic cells into the lymph nodes draining skin sites exposed to attenuated cercariae of Schistosoma mansoni in guinea-pigs

We compared temporal changes in the cell composition of the skin-draining lymph nodes (SLN) in guinea-pigs exposed percutaneously to normal or attenuated cercariae of Schistosoma mansoni. Different populations were analysed by flow cytometry of double-stained cells by monoclonal antibodies to the major histocompatibility complex class II molecule and lymph node cells of guinea-pigs. Exposure to S. mansoni caused a marked increase in the proportion of B cells and dendritic cells (DC) on day 2, reaching a peak number on day 4. These changes were comparable in both infected and vaccinated animals exposed to normal or attenuated parasites, respectively. Total number of DC, however, showed different kinetics; in infected animals, the number peaked on day 2 and then gradually declined, whereas it reached a higher peak on day 4 in vaccinated animal. Daily injection of bromo-deoxyuridine after exposure to the parasite reduced the total number of DC in the SLN on day 4. A reduction in DC counts in the contralateral side SLN was also evident in vaccinated animals. Our results indicate that a significant number of newly formed DC are recruited to the skin by 4th day of vaccination, followed by increased efflux to the SLN. It is possible that retention of attenuated S. mansoni in the skin may cause accelerated recruitment of newly formed DC from the bone marrow, and facilitate transport and processing of antigens highly expressed on attenuated parasites.     

A Simple, 10-minute Procedure for Transforaminal Injection under Ultrasonic Guidance to Effect Cervical Selective Nerve Root Block

The aim is to provide a detailed procedure of a simple and 10-minute cervical nerve root block (CNRB) under ultrasonic guidance, and to report the clinical outcomes, disorders, and complications. Records of patients who had undergone CNRB, were reviewed under ultrasonic guidance at the hospital from 2010 through 2012. The procedure is described in detail. Arm and shoulder pain was evaluated by use of the visual analogue scale (VAS). Forty-three patients agreed to undergo CNRB under ultrasonic guidance. Nerve roots from C5 to C8 were affected in 41, and these nerve roots were readily distinguished. Two of the 43 participants did not receive injections because impediments in visualizing the affected nerve root. Of the 41 who received injections, radicular pain immediately disappeared in 39, who continued to feel pain relief 1 month later. However, pain recurred in 15 patients (38%), of whom 11 underwent cervical spine surgery. The rest of 24 patients felt sustained pain relief longer than 3 months after the injection, significantly. Although one patient had recurrent radicular pain 10 months later, the pain could be controlled by medication. At the final follow-up periods, 17.2 (10–24 months), the median VAS score of the patients, 23 (0 to 71 mm), was significantly improvement (P = 0.001) in comparison to before injection 88 (range; 56–100). No complications occurred. The cervical nerve root block under ultrasonic guidance simply, safely, and efficaciously decreased radicular pain for 17.2 months in 62% patients with intolerable radicular pain.     

Update on Stent Implantation in Acute Myocardial Infarction

Primary stent implantation in acute myocardial infarction (AMI) is defined as the intentional (not rescue) implantation of intracoronary stent(s) to the culprit lesion of AMI during emergency catheterization. All available data showed that this strategy has favorable short- and long-term clinical effects compared to primary balloon angioplasty.     

Immunogenicity and reactogenicity of the component acellular pertussis vaccine produced by a combination of column purified pertussis toxin and filamentous haemagglutinin

This is the report on a prospective, single blind, comparative study of a component acellular pertussis vaccine produced by a combination of detoxified, column purified pertussis toxin (PT) and filamentous hemagglutinin (FHA) combined with diphtheria and tetanus toxoids (DTcaP) and the traditional acellular pertussis vaccine produced with essentially the same method as described by Sato with DT (DTaP) of the same manufacturer. A total of 616 infants and children received DTcaP and a total of 289 received DTaP. In all age groups for both vaccines values of serum antibodies to PT and FHA after two doses of the vaccines were comparable to those of convalescent sera. Incidences of systemic and local reactions were, in general, not greatly different between DTcaP and DTaP recipients. In Japan the use of traditional acellular vaccines replaced whole cell vaccines in 1981. Protective antigens of Bordetella pertussis have now been specified and thus component vaccines have become theoretically possible. This is the first component vaccine which has been developed in Japan. Several other component vaccines are now under investigation in the world.     

Interactions of Endotoxin with Cortisol and Acute Phase Proteins in Septic Shock Neonates

ABSTRACT. CRP, α1-acid glycoprotein and haptoglobin were studied in 13 septic shock neonates. Endotoxin was recovered from eight infants. Serum Cortisol concentration from infants with en-dotoxemia (917 ± 596 ng/ml) was significantly higher than that from infants without en-dotoxemia (398 ± 239 ng/ml). Serum Cortisol correlated well with immature neutrophil counts denned as the unit "band/neutrophil". Increased Cortisol level and immature neutrophil counts preceded the elevation of CRP, α1-acid glycoprotein and haptoglobin in four extremely premature neonates. We conclude that positive interactions between endotoxin, Cortisol and acute phase protein synthesis are present in the initial period of infection, and delayed acute phase protein synthesis is suspected in extremely premature neonates.     

Moyamoya disease associated with bilateral renal artery stenosis

Recent research has suggested that an association exists between moyamoya disease and fibromuscular dysplasia which involves systemic vessels, including renal arteries. We report a 3 year old girl with moyamoya disease associated with bilateral renal artery stenosis. This case may support the common etiology of these two clinical conditions. To our knowledge this is the youngest case of moyamoya disease associated with bilateral renal artery stenosis.