Serum from minimal change patients in relapse increases CD80 expression in cultured podocytes

Background

Minimal change disease (MCD) is the most common cause of nephrotic syndrome in children and is associated with the expression of CD80 in podocytes and the increased excretion of CD80 in urine. We hypothesized that serum from patients with MCD might stimulate CD80 expression in cultured podocytes.

Methods

Sera and peripheral blood mononuclear cells (PBMCs) were collected from subjects with MCD in relapse and remission and from normal controls. Immortalized human podocytes were incubated with culture media containing patient sera or supernatants from patient and control PBMC cultures. CD80 expression was measured by quantitative PCR and western blot analysis.

Results

Sera collected from patients with MCD in relapse, but not in remission, significantly increased CD80 expression (mean ± standard deviation: 1.8?±?0.7 vs. 0.8?±?0.2; p?<?0.004) and CD80 protein secretion by podocytes (p?<?0.05 between relapse and normal controls). No such CD80 increase was observed when podocytes were incubated with supernatants of PBMC cultures from patients in relapse.

Conclusions

Sera from MCD patients in relapse, but not in remission, stimulated CD80 expression in cultured podocytes. Identifying this factor in sera could provide insights into the pathogenesis of this disorder. No role in CD80 expression by podocytes was found for cytokines released by PBMCs.     

Osteocyte death during orthodontic tooth movement in mice

Objective:To investigate the time course of osteocyte death in a mouse model of orthodontic tooth movement (OTM) and its association to the caspase-3 activation pathway and osteoclast formation.Materials and Methods:Twenty-five male wild type CD-1 mice (8–12 weeks old) were loaded with an orthodontic appliance. A spring delivering 10–12 g of force was placed between the right first molar and the incisor to displace the first molar mesially. The contralateral unloaded sides served as the control. The animals were equally divided into five different time points: 6, 12, 24, and 72 hours and 7 days of orthodontic loading. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, caspase-3 immunostaining, and tartrate-resistant acid phosphatase (TRAP) staining was performed on histologic sections of the first molars. The labeling was quantified in osteocytes on the compression side of the alveolar bone at each time point.Results:TUNEL labeling significantly increased at 12, 24, and 72 hours after orthodontic loading; the peak was observed at 24 hours. Elevated caspase-3 labeling was noted at 12, 24, and 72 hours and 7 days after loading, although the increase was not significant. Significant osteoclast formation was initially evident after 72 hours and progressively increased up to 7 days.Conclusions:Osteocyte death during OTM peaks at 24 hours, earlier than initial osteoclast activation. However, only a slight trend for increased caspase-3 activity suggests that other mechanisms might be involved in osteocyte death during OTM.     

Carnosine as a protective factor in diabetic nephropathy: association with a leucine repeat of the carnosinase gene CNDP1

The risk of diabetic nephropathy is partially genetically determined. Diabetic nephropathy is linked to a gene locus on chromosome 18q22.3-q23. We aimed to identify the causative gene on chromosome 18 and to study the mechanism by which the product of this gene could be involved in the development of diabetic nephropathy. DNA polymorphisms were determined in 135 case (diabetic nephropathy) and 107 control (diabetes without nephropathy) subjects. The effect of carnosine on the production of extracellular matrix components and transforming growth factor-beta (TGF-beta) after exposure to 5 and 25 mmol/l d-glucose was studied in cultured human podocytes and mesangial cells, respectively. A trinucleotide repeat in exon 2 of the CNDP1 gene, coding for a leucine repeat in the leader peptide of the carnosinase-1 precursor, was associated with nephropathy. The shortest allelic form (CNDP1 Mannheim) was more common in the absence of nephropathy (P = 0.0028, odds ratio 2.56 [95% CI 1.36-4.84]) and was associated with lower serum carnosinase levels. Carnosine inhibited the increased production of fibronectin and collagen type VI in podocytes and the increased production of TGF-beta in mesangial cells induced by 25 mmol/l glucose. Diabetic patients with the CNDP1 Mannheim variant are less susceptible for nephropathy. Carnosine protects against the adverse effects of high glucose levels on renal cells.     

A six-year study on Vibrio cholerae in southeastern Iran

Cholera continues to be an important public health problem among many poorer communities. In order to determine the epidemiology of Vibrio cholerae in southeastern Iran, 3,594 patients with watery diarrhea, who were referred to the hospitals from Zabol city and 45 neighboring rural populations of Sistan-Blouchestan province, were investigated over a period of 6 years (1997 - 2002). V. cholerae strains were isolated from 362 samples (10.07%). Isolation of V. cholerae in this sample decreased from 22.47% in 1997 to 0% in 2002. Individuals of all ages and social and economic strata were affected. Among the patients with cholera in the present study, only 24 (6.6%) lived in an urban area; 270 (74.6%) of the patients had been referred from rural areas, and the remaining 68 (18.8%) were from neighboring Afghanistan. V. cholerae O1 Ogawa and NAG vibrios were found in 92.8 and 7.2% of patients, respectively. Among the 362 samples, 244 were collected from inpatients and 118 were from outpatients. Twelve of these patients died because of the severity of their disease, severe dehydration and electrolytes imbalance. The priorities for cholera control remain public health interventions through improved water and sanitation, improved surveillance and access to health care facilities, and further development of appropriate vaccines.     

Skin picking and sleep disturbances: relationship to anxiety and need for research

Pathological excoriation (PE) or skin picking is seen in nearly 2% of patients attending dermatology clinics and is often associated with anxiety, stress and frequent help-seeking behaviors. While anxiety and stress are thought to cause poor sleep in the general population, not all anxious people, even those with disabling anxiety disorders, necessarily suffer from insomnia or other sleep problems. The relationship between anxiety symptoms and poor sleep, therefore, remains unclear and sleep quality in PE is unknown. We examined the sleep quality and levels of anxiety in dermatological patients with PE. Dermatological patients with (n = 10) and without (n = 10) PE and healthy controls (n = 10) were assessed on standardized and validated measures of subjective sleep quality [Pittsburgh Sleep Quality Index (PSQI)], anxiety (Spielberger State and Trait Anxiety Inventory; modified Zung Anxiety Scale), stress (Perceived Stress Scale) and work and social disability [Sheehan Disability Inventory subscale (SDI-4)]. Patients with dermatological complaints as a group reported poorer sleep quality, higher scores on Spielberger State and Zung anxiety, perceived stress, and SDI-4. Among both groups of dermatological patients, only the PE group had significantly poor sleep, high anxiety, and perceived stress compared to healthy controls. In the dermatological patients with PE, PSQI-global scores were significantly positively correlated to Spielberger State and Zung Anxiety scores. Dermatological patients with PE are more anxious and have poorer subjective sleep compared to dermatological patients without PE and healthy. Future research is needed to elucidate these relationship factors and to develop new behavioral and drug treatments for the management of PE.     

Unsuspected recurrent pituitary adenoma presenting as an orbital mass

PURPOSE: Orbital invasion of pituitary tumors is rare and usually accompanied by optic nerve head pallor and visual loss. We describe a case of unilateral massive orbital invasion by a recurrent pituitary tumor with preserved visual acuity and normal optic nerve appearance. METHODS: Case report. RESULTS: Progressive proptosis developed 15 years after transphenoidal removal of a pituitary tumor. Based on the radiological appearance and the clinical history, the patient was suspected to have a sphenoid wing meningioma secondary to previous radiation treatment. A combined neurosurgical and orbital approach was used to remove the intraorbital mass, which extended from the cranial cavity through the superior orbital fissure and the optic canal. Histopathologic examination demonstrated a recurrent nonsecreting pituitary adenoma. CONCLUSIONS: Orbital extension of a recurrent pituitary adenoma should be considered in the differential diagnosis of progressive proptosis even in the absence of significant optic neuropathy.     

Recent advances of animal model of focal segmental glomerulosclerosis

In the last decade, great advances have been made in understanding the genetic basis for focal segmental glomerulosclerosis (FSGS). Animal models using specific gene disruption of the slit diaphragm and cytoskeleton of the foot process mirror the etiology of the human disease. Many animal models have been developed to understand the complex pathophysiology of FSGS. Therefore, we need to know the usefulness and exact methodology of creating animal models. Here, we review classic animal models and newly developed genetic animal models. Classic animal models of FSGS involve direct podocyte injury and indirect podocyte injury due to adaptive responses. However, the phenotype depends on the animal background. Renal ablation and direct podocyte toxin (PAN, adriamycin) models are leading animal models for FSGS, which have some limitations depending on mice background. A second group of animal models were developed using combinations of genetic mutation and toxin, such as NEP25, diphtheria toxin, and Thy1.1 models, which specifically injure podocytes. A third group of animal models involves genetic engineering techniques targeting podocyte expression molecules, such as podocin, CD2-associated protein, and TRPC6 channels. More detailed information about podocytopathy and FSGS can be expected in the coming decade. Different animal models should be used to study FSGS depending on the specific aim and sometimes should be used in combination.