A call for a gender specific approach to address the worldwide cardiovascular burden

Cardiovascular diseases (CVD) among non-communicable diseases are already a major public health challenge worldwide. A further increase in CVD is projected to occur over the next 25 years as a result of both adverse lifestyle changes and demographic shifts in the population age profile. The adverse impact of these health problems will affect women in particular, given the steady rise in the proportion of the aging population that will be women.The critical issue presently in the management of CVD is that we are not even adequately using the data that are available. Women still remain unaware that they are at risk, and information about women is not easily accessible to their physicians. This is a global issue and the need remains for worldwide initiatives with greater vigilance to identify these factors and make efforts to control them effectively.Currently, in scientific research, it is expected that the results of clinical research be analyzed for sex differences, sex- and gender-appropriateness, and sex- and gender-specific approaches for prevention, diagnosis, treatment, and counseling. To address the care discrepancy, the global community needs to develop a conducive environment within a comprehensive policy and operational framework to achieve favorable lifestyles, and CVD risk factor reduction for both men and women.     

Divergent expression and localization of aquaporin 5, an exocrine-type water channel,in the submandibular gland of Sprague-Dawley rats

By Western blot analysis, the expression level of aquaporin (AQP) 5 in the submandibular gland (SMG) was found to be different among individual rats of the Sprague-Dawley (SD) strain. Such differences were observed for AQP5 but not for AQP1 and consequently the SD strain was divided into two groups, one expressing a high level of AQP5 and the other a low one. The difference in average intensity of expression between the two groups was more than twofold. Immunohistochemical analysis of the SMG demonstrated that the AQP5 protein was localized in the basal and apical/lateral plasma membrane of acinar cells in rats expressing the high level of AQP5. In the rat expressing the low level, however, this channel protein was localized strongly in the apical/lateral plasma membrane, but only very weakly in the basal membrane of the acinar cells. Such a diverse localization of AQP5 was confirmed by Western blotting as well. Breeding between brother and sister was repeated for two times within high expressers and low expressers to obtain the third generation progenies (F2); the AQP5 level of the SMG in the third generation (F2 rats) from high expressers was significantly higher than the F2 from low expressers. Our present study suggests the existence of genetic variation in the expression of a water channel protein, AQP5, in rats.     

A deletion–insertion mutation in the phosphomannomutase 2 gene in an African American patient with congenital disorders of glycosylation‐Ia

Congenital disorders of glycosylation (CDG) are a group of metabolic disorders with multisystemic involvement characterized by abnormalities in the synthesis of N‐linked oligosaccharides. The most common form, CDG‐Ia, resulting from mutations in the gene encoding the enzyme phosphomannomutase (PMM2), manifests with severe abnormalities in psychomotor development, dysmorphic features and visceral involvement. While this disorder is panethnic, we present the first cases of CDG‐Ia identified in an African American family with two affected sisters. The proband had failure to thrive in infancy, hypotonia, ataxia, cerebellar hypoplasia and developmental delay. On examination, she also exhibited strabismus, inverted nipples and an atypical perineal fat distribution, all features characteristic of CDG‐Ia. Direct sequencing demonstrated that the patient had a unique genotype, T237M/c.565‐571 delAGAGAT insGTGGATTTCC. The novel deletion–insertion mutation, which was confirmed by subcloning and sequencing of each allele, introduces a stop codon 11 amino acids downstream from the site of the deletion. The presence of this deletion–insertion mutation at cDNA position 565 suggests that this site in the PMM2 gene may be a hotspot for chromosomal breakage. Published 2002 Wiley‐Liss, Inc.     

Leishmania promastigote membrane antigen-based enzyme-linked immunosorbent assay and immunoblotting for differential diagnosis of Indian post-kala-azar dermal leishmaniasis

Diagnosis of post-kala-azar dermal leishmaniasis (PKDL), caused by Leishmania donovani, is difficult, as the dermal lesions are of several types and resemble those caused by other skin diseases, especially leprosy. Since the disease generally appears very late after the clinical cure of kala-azar in India, it is also difficult to correlate PKDL with a previous exposure to L. donovani. Very few attempts have been made so far to diagnose PKDL serologically, and the diagnostic methods vary in their sensitivities and specificities. Diagnosis of PKDL through sophisticated PCR methods, although highly sensitive, has limited practical use. We have developed a serodiagnostic method using an enzyme-linked immunosorbent assay to detect specific immunoglobulin (Ig) isotypes and IgG subclass antibodies in the sera of Indian PKDL patients. Our assay, which uses L. donovani promastigote membrane antigens, was 100% sensitive for the detection of IgG and 96.7% specific for the detection of IgG and IgG1. Optical density values for individual patients, however, demonstrated wide variations. Western blot analysis based on IgG reactivity could differentiate patients with PKDL from control subjects, which included patients with leprosy, patients from areas where kala-azar is endemic, and healthy subjects, by the detection of polypeptides of 67, 72, and 120 kDa. The recognition patterns of the majority of serum samples from patients with PKDL were also distinct from those of the serum samples from patients with visceral leishmaniasis (VL), at least for a 31-kDa polypeptide. To further differentiate patients with PKDL from those with active and cured VL, we analyzed the specific titers of the Ig isotypes and IgG subclasses. High levels of IgG, IgG1, IgG2, and IgG3 antibodies significantly differentiated patients with PKDL from patients cured of VL. The absence of antileishmanial IgE and IgG4 in patients with PKDL differentiated these patients from those with active VL. These results imply intrinsic differences in the antibodies generated in the sera from patients with PKDL and VL.     

Oxidative reactions in the tear fluid of patients suffering from dry eyes

Purpose: To evaluate whether products of oxidative and inflammatory reactions are detectable in the tear fluid of patients suffering from dry eyes. Methods: The tear fluid of 217 patients (397 eyes) was sampled. Criteria for grouping of the patients were (1) basic secretion test (sicca l: BST = 0–5 mm, n = 78 eyes; sicca 2: BST = 6–10 mm, n = 109 eyes) and (2) subjective symptoms (normal BST, burning, foreign body sensations, tearing, dryness of the eyes: n = 78 eyes). One group of healthy patients (normal BST, n = 132 eyes) served as controls. Lipid peroxide levels and myeloperoxidase activity, as parameters for oxidative tissue damage and inflammatory activity, were determined in the tear fluid. Those patients whose consent could be obtained were subjected to the rose bengal test (sicca 1: 56 eyes; sicca 2: 97 eyes; subjective symptoms: 44 eyes; controls: 49 eyes). The correlation between BST and rose bengal test results was calculated. Results: Lipid peroxides were significantly (P < 0.05) higher in the groups sicca 1 and subjective symptoms than in healthy controls, as was the inflammatory activity in groups sicca 1, sicca 2 and subjective symptoms. Additionally, the inflammatory activity in the group sicca 1 was significantly (P < 0.05) higher than in the groups sicca 2 and subjective symptoms. No evidence of a significant correlation between BST and rose bengal test results was observed. Conclusions: Both oxidative tissue damage and polymorphonuclear leukocytes indicating an oxidative potential occur in the tear film of patients suffering from dry eyes. These reactions lead to severe damage of the involved tissue. Free radicals and inflammation may be involved in the pathogenesis or in the self-propagation of the disease.     

A Three-Dimensional Developmental Measurement of the Temporomandibular Joint

This article presents an anthropologic study of the growth and developmental changes that occur within the bony components of the temporomandibular joint. The material used was provided by the Department of Physical Anthropology of the Smithsonian Institution Museum of Natural History, Washington, D.C.

Based on a Class I normal occlusion, the authors selected a total of 100 skulls with mandibles from the Aleutian Islands collection. These skulls, which were from 2-to 20-year-old subjects, were divided into four age groups. The approximate age of each skull was determined by charts based on eruption sequence, the number of permanent teeth present, and suture closure.

Anatomic landmarks and anthropologic techniques were used to make direct linear measurements on the bony components of the 200 temporomandibular joints. Three-dimensional measurements were made on the condyles, fossae, and articular eminences of each skull.

Several variables were chosen for statistical analysis: (1) The size of the individual components of the TMJ within each age group. (2) The changes with age in the anteroposterior, medial-lateral, and vertical dimensions of the individual TMJ components. (3) Asymmetries in size between the right and the left TMJ components. (4) The interrelationship of the individual TMJ components as seen in their growth changes.

The results obtained from the various measurements used in this study were compared to the findings of a number of earlier studies.     

Immunogenicity and efficacy of a bivalent DNA vaccine containing LeIF and TSA genes against murine cutaneous leishmaniasis

There is no effective vaccine for the prevention and elimination of leishmaniasis. For this reason, we assessed the protective effects of DNA vaccines containing LeIF, TSA genes alone, or LeIF–TSA fusion against cutaneous leishmaniasis pEGFP‐N1 plasmid (empty vector) and phosphate buffer saline (PBS) were used as control groups. Therefore, cellular and humoral immune responses were evaluated before and after the challenge with Leishmania major. Lesion diameter was also measured 3–12 weeks after challenge. All immunized mice with plasmid DNA encoding Leishmania antigens induced the partial immunity characterized by increased IFN‐γ and IgG2a levels compared with control groups (p < 0.001). Furthermore, the immunized mice showed significant reduction in mean lesion sizes compared with mice in empty vector and PBS groups (p < 0.05). The reduction in lesion diameter was 29.3%, 34.1%, and 46.2% less in groups vaccinated with LeIF, TSA, and LeIF‐TSA, respectively, than in PBS group at 12th week post infection. IFN/IL‐4 and IgG2a/IgG1 ratios indicated that group receiving LeIF–TSA fusion had the highest IFN‐γ and IgG2a levels. In this study, DNA immunization promoted Th1 immune response characterized by higher IFN‐γ and IgG2a levels and also reduction in lesion size. These results showed that a bivalent vaccine containing two distinct antigens may induce more potent immune responses against leishmaniasis.