Insulin-like Growth Factor and its Therapeutic Potential for Diabetes Complications - Mechanisms and Metabolic Links: A Review

BACKGROUNDThe insulin-like growth factor (IGF) system is an important system in normal physiological functioning of the body. In diabetes mellitus, alterations of IGF-binding protein (IGFBP) levels have been described, mainly in vascular complications.AIMThe aim of this review was to explore the role of the IGF system in reducing diabetes complications and its role as potential therapeutic target.RESULTSIGF-1 plays a role in neuronal growth and developmental processes. Low concentrations of IGF-1 have been associated with neuropathy and other diabetes complications. Moreover, impaired IGF synthesis and function may result in cellular senescence and impaired vascular endothelial proliferation, adhesion, and integration. Of note, high IGF-1 bioavailability may prevent or delay the inception of diabetes-associated complications in diabetes patients. The mechanism of normal functioning IGF-1 is induced by increasing nitric oxide synthesis and potassium ion channel opening in cardiovascular physiology, which improves impaired small blood vessel function and reduces the occurrence of diabetes complications associated with reduced concentrations of IGF-1.CONCLUSIONSIGF may be considered an alternative therapy for diabetes and diabetes-associated complications. Therefore, future studies should focus on the mechanism of action and therapeutic potential of IGFs in reducing the risk of development and progression of the disease in different clinical settings.     

Cases of advanced abdominal pregnancies one of which was with viable fetus

Cases of advanced abdominal pregnancies, which were admitted to Gondar College of Medical sciences teaching hospital, North-western Ethiopia, in the years 2000 and 2001, are described, and the challenges in the diagnosis and management discussed One of these pregnancies resulted in the delivery of a viable fetus.     

Pattern of skin diseases at the University teaching hospital, Addis Ababa, Ethiopia

BACKGROUND AND OBJECTIVE: Skin diseases are among the leading causes of hospital visits in Ethiopia. An analysis was performed to describe the pattern of skin diseases at a teaching hospital in Addis Ababa, Ethiopia. PATIENTS AND METHODS: All consecutive new patients seen at the dermatologic referral clinic of Black Lion Teaching Hospital (BLH) from June 1995 to July 1997 were included in this prospective analysis. The clinical examinations were performed by the author, so that uniformity of diagnosis and classification is assured. RESULTS: A total of 1505 patients were assessed; 1093 (72. 6%) were in the age group 21-40 years, and the female to male ratio was 1.2 to 1. The most common skin diseases were allergic skin diseases (25.5%), infections (25.4%), the photodermatoses (22.9%), followed by papulosquamous diseases (11.4%) and pruritis of unknown origin (3.3%). Skin manifestations of collagen diseases were less common findings (0.7%). CONCLUSIONS: The pattern of skin diseases observed in this analysis shows that allergic and infectious causes account for three-quarters of skin problems. Emphasis should be given to this group of common skin diseases at all levels of health care so that proper diagnosis, treatment, and referral can be practiced.     

Protective and antifecundity effects of Sm-p80-based DNA vaccine formulation against Schistosoma mansoni in a nonhuman primate model

Schistosomiasis is an important parasitic disease for which there is no available vaccine. We have focused on a functionally important antigen of Schistosoma mansoni, Sm-p80, as a vaccine candidate because of its consistent immunogenicity, protective potential and antifecundity effect observed in murine models; and for its pivotal role in the immune evasion process. In the present study we report that an Sm-p80-based DNA vaccine formulation confers 38% reduction in worm burden in a nonhuman primate model, the baboon (Papio anubis). Animals immunized with Sm-p80–pcDNA3 exhibited a decrease in egg production by 32%. Sm-p80 DNA elicited specific immune responses that include IgG; its subtypes IgG1 and IgG2; and IgM in vaccinated animals. Peripheral blood mononuclear cells (PBMCs) from immunized animals when stimulated in vitro with Sm-p80 produced appreciably more Th1 response enhancing cytokines (IL-2, IFN-γ) than Th2 response enhancing cytokines (IL-4, IL-10). PBMCs produced appreciably more spot-forming units for INF-γ than for IL-4 in enzyme-linked immunosorbent spot (ELISPOT) assays. Overall it appears that even though a mixed (Th1/Th2) type of humoral antibody response was generated following immunization with Sm-p80; the dominant protective immune response is Th1 type. These data reinforce the potential of Sm-p80 as an excellent vaccine candidate for schistosomiasis.     

Schistosoma mansoni antigen Sm-p80: Prophylactic efficacy of a vaccine formulated in human approved plasmid vector and adjuvant (VR 1020 and alum)

Schistosomiasis is an important parasitic disease. Consensus is developing now that ideal control methods of the disease should be based on an integrated approach incorporating drug treatment, sanitation improvement, education, and an effective vaccine. With regards to the vaccine development, Sm-p80 has been shown to be a promising and strong immunogenic vaccine candidate. In the present study, Sm-p80-based vaccine formulated in alum was tested for its prophylactic efficacy in a mouse model. It was observed that vaccination using heterologous prime boost (DNA prime followed by boost with protein formulated in alum) and homologous prime boost (both prime and boost with protein formulated in alum) approaches, resulted in 61% and 55% reduction in worm burden, respectively. The protection was directly correlated with the induction of high titers of antibody responses that mainly included IgG, its isotypes, and IgM. In addition, both of the immunization approaches triggered a mixed Th1 and Th2 type response. Some involvement of Th17 specific immune response was also detected as indicated by the up-regulation of relevant cytokines. These results reinforce the potential of Sm-p80 as a viable vaccine candidate.     

Role of antibodies in Sm-p80-mediated protection against Schistosoma mansoni challenge infection in murine and nonhuman primate models

Schistosomiasis is an important public health concern in more than 76 developing countries. Advent of an anti-schistosome vaccine would undoubtedly add to the existing control measures and may eventually help in the elimination of this disease. In the present study we have attempted to dissect the role(s) of antibodies in Sm-p80 mediated protection by intravenously transferring pooled sera from mice immunized with Sm-p80-pcDNA3 or purified IgG from baboons immunized with Sm-p80-pcDNA3, into naïve C57BL/6 mice, respectively, prior to challenge with cercariae. The passive transfer of antibodies from protected mice (homologous transfers) as well as transfer of total IgG from baboons (heterologous transfers), into naïve mice showed statistically significant reductions in worm burden and in the number of eggs in the tissues. Immunizations of antibody knockout mice (μMt−/−; B10.129S2 (B6)-Igh-6^tm1Cgn/J) with recombinant Sm-p80 in the presence of CpG-motif oligodeoxynucleotides as an adjuvant, resulted in substantial reduction of Sm-p80-mediated protection, compared to C57BL/6 (normal) control group of mice. Down regulation of cytokines that have important effects on B cell proliferation as well as the recovery of higher number of parasites in antibody knockout indicated a significant role(s) of antibodies in Sm-p80-mediated protection against Schistosoma mansoni in mice. In toto, these studies appear to suggest that antibodies play a significant role in Sm-p80 mediated protection.