Effects of potassium citrate/citric acid intake in a mouse model of polycystic kidney disease

The kidney function in a model of autosomal dominant polycystic kidney disease (PKD), the Han:SPRD rat, is dramatically improved by chronic ingestion of a solution of potassium citrate and citric acid (KCitr). This study investigated whether this treatment would also be beneficial in the pcy/pcy mouse, a model of autosomal recessive PKD. Starting at 1 month of age, male CD-1 pcy/pcy and normal CD-1 mice were provided with a solution of 55 mM K(3) citrate/67 mM citric acid or tap water to drink. The pcy/pcy mice on the KCitr solution failed to grow normally and showed elevated plasma urea levels when compared to water-drinking littermates. Growth of normal CD-1 mice was not affected by KCitr intake. The pcy/pcy mice were then provided with a more dilute solution of KCitr to drink: this resulted in greater kidney wet and dry weights and a higher kidney weight/body weight ratio, but no beneficial effects. We conclude that pcy/pcy mice cannot tolerate a high level of KCitr intake and that a lower level is of no benefit. Whether KCitr therapy would be helpful in patients with PKD is still an open question.     

A new surgical technique for ocular fixation in congenital third nerve palsy.

PURPOSE: To present a new technique of ocular fixation to restore and maintain the ocular alignment in primary position for patients with total third nerve paralysis. METHOD: We fixated the globe (medial rectus muscle insertion) to the medial palpebral ligament insertion at the anterior lacrimal crest by using nonabsorbable 5-0 polyester sutures in a prospective study of 5 patients (5 eyes) with congenital total third nerve paralysis. A large recession of the lateral rectus muscle (12 to 16 mm) was also performed in four patients. RESULTS: Four patients achieved satisfactory ocular alignment and one patient had residual exotropia. After an initial exotropic shift, no significant change in ocular alignment was observed during the follow-up period of 6 to 9 months. Mild fullness and congestion over the medial rectus muscle area was observed in the immediate postoperative period in all the patients, which resolved in about two months time. CONCLUSION: This technique of ocular fixation is easy, safe, and effective for the management of exotropia secondary to total third nerve paralysis.     

Effect of presensitization with BCG and Mycobacterium leprae on granuloma formation to M. leprae

Granulomas which develop in draining lymph nodes, following the intradermal injection of cobalt-irradiated Mycobacterium leprae into the ear of the guinea pig 2 and 5 weeks earlier, were studied in animals which had been presensitized with BCG vaccine or M. leprae and compared with granulomas that developed in previously unsensitized guinea pigs. Presensitization with mycobacteria accelerated the development of the granulomas. Granulomas in previously unsensitized guinea pigs were found ultrastructurally to contain phagocytosing macrophages similar to those in lepromatous leprosy, and M. leprae presensitization did not alter the type of granuloma found. Those in BCG-presensitized guinea pigs contained secretory epithelioid cells with rough endoplasmic reticulum similar to those found in borderline tuberculoid leprosy or reversal reactions. The significance of these findings in relation to the current use of vaccines in leprosy is discussed.     

Association of IL‐1β +3954 C/T and IL‐10‐1082 G/A Cytokine Gene Polymorphisms with Susceptibility to Tuberculosis

Tuberculosis (TB) constitutes the major cause of death due to infectious diseases. Cytokines play a major role in defence against Mycobacterium tuberculosis infection. Polymorphisms in the genes encoding various cytokines have been associated with tuberculosis susceptibility. Household contacts (HHC) are at increased risk of developing the disease. In this study, we examined the association of IL‐1β and IL‐10 cytokine gene polymorphisms with risk of developing tuberculosis in TB patients, their HHC and healthy controls (HC) using JavaStat and SPSS. Multifactor dimensionality reduction (MDR) analyses were performed to explore the potential gene–gene interactions. The genotype and allele frequencies of IL‐1β +3954C/T polymorphism did not vary significantly between TB patients and HC. GG (P < 0.005, OR = 0.219 and 95% CI = 0.059–0.735) and GA (P < 0.0001, OR = 2.938 and 95% CI = 1.526–5.696) genotypes of IL‐10‐1082 G/A polymorphism were found to be significantly associated with patients versus HC. HHC with CC (P < 0.03, OR = 1.833 and 95% CI = 1.1–3.35) genotype in IL‐1β and GA (P < 0.0001, OR = 4.612 and 95% CI = 2.225–9.702) genotype in IL‐10 were at increased risk of developing tuberculosis. MDR tests revealed high‐risk genotypes in IL‐1β and IL‐10 based on the association model. Our results demonstrate that the polymorphisms of IL‐1β and IL‐10 genes may be valuable markers to predict the risk for the development of TB in household contacts.