Diagnosing Diabetic Neuropathy: Something Old, Something New

There are potentially many ways of assessing diabetic peripheral neuropathy (DPN). However, they do not fulfill U.S. Food and Drug Administration (FDA) requirements in relation to their capacity to assess therapeutic benefit in clinical trials of DPN. Over the past several decades symptoms and signs, quantitative sensory and electrodiagnostic testing have been strongly endorsed, but have consistently failed as surrogate end points in clinical trials. Therefore, there is an unmet need for reliable biomarkers to capture the onset and progression and to facilitate drug discovery in DPN. Corneal confocal microscopy (CCM) is a non-invasive ophthalmic imaging modality for in vivo evaluation of sensory C-fibers. An increasing body of evidence from multiple centers worldwide suggests that CCM fulfills the FDA criteria as a surrogate endpoint of DPN.

Differences in molecular pathologic characteristics of pancreatic adenocarcinoma between Egyptian and Moroccan patients

Pancreatic cancer has not been well studied, especially in developing countries. We studied the variations in genetic mutations in pancreatic adenocarcinoma between Moroccan and Egyptian populations. The molecular pathology of 30 tumors from a large hospital in Casablanca, Morocco were examined and compared with the findings of 44 tumors from the Gharbiah Governate in Egypt. K-ras mutations in codons 12 and 13 in addition to p53 mutations in exons 5-8 were evaluated. Overall, differences in the rates of K-ras mutations were not statistically significant [48.00 and 34.09%, respectively]; however differences in rates of p53 mutations were statistically significant with p53 mutations more common in Moroccan tumors than in Egyptian tumors [46.67 and 16.28%, respectively]. G ->T mutations of the K-ras gene were most commonly seen Egyptian tumors, whereas G -> A mutations were the most common type of mutations in Moroccan tumors. Logistic regression analysis showed that a p53 mutation in any exon as well as a p53 mutation in exon 5 predicted the country of residence and those mutations occurred more frequently in Moroccan patients. Our study shows that differences exist within the Arab population in the molecular pathology of both the K-ras and p53 genes. Further studies are necessary to clarify the differences in molecular pathways of pancreatic cancer in the Middle East and to investigate the role of environmental and/or genetic factors related to those pathways

Effect of melatonin on some bone turnover markers in ovarectomized rats

This study was carried out to evaluate the effect and the mechanism of action of melatonin on some bone markers in ovarectomized bone loss in rats. 32 female albino rats underwent either bilateral laparotomy [sham, n=8] or bilateral ovarectomy [Ovx, n=24]. The Ovx rats were divided into 3 groups, each of 8 rats; Vehicle-treated [Ovx], estrogen-treated [E2] and melatonin-treated [Mlt] group. After 14 weeks treatment, blood and urine were collected. Serum osteoprotegerin [OPG], inhibin, follistatin, and alkaline phosphatase [ALPase] were determined as bone markers. In addition, urinary Deoxypyridinoline [uDPD] was assayed. Serum OPG, inhibin and follistatin levels significantly decreased upon Ovx. They increased upon either treatment with E2 or Mlt with non- significant difference in between as compared to Ovx group. In addition, serum ALPase and uDPD significantly increased on Ovx and decreased with either therapy as compared to Ovx one with non- significant difference between both therapies. The results revealed that administration of Mlt inhibited high bone turnover and prevented calcium loss in ovarectomized rats. This may be through increasing OPG, inhibin and/or follistatin levels. Mlt could be a candidate for the treatment of postmenopausal osteoporosis

Stress-induced factors colinked to chronic hepatic insult inducing fatigue influence of combined therapy

Objectives: The study aimed to evaluate the benefits of combined therapeutic strategy of multidisciplinary mechanisms in management of cases subjected to chronic hepatic insult inducing fatigue. They were co-linked to perturbations of immune, metabolic and hepatotoxic environmental stress-induced factors posed by cigarette smoking in subjects with Schistosomal hepatic fibrosis infected with hepatitis E [HEV] and/or of chronic hepatitis B [HBV] co-infection. Study Design Selected cases involved fifty cigarette smoker subjects with schistosomal hepatic fibrosis suffering from fatigue symptoms they included twenty five cases with HEV who were categorized into those with history of chronic HBV [Gr. Ia] or without [Gr. IIa] and 25 allied subjects without HEV with of either chronic HBV [Gr, IIIa] or recurrent schisosomal infection [Gr. IVa]. Control group [Gr. V] composed of 10 healthy nonsmokers were also included. The provided therapeutic regimen for 6 months had included ginko bilopa, ginsing, royal jelly, echinacea extracts and sylimarin. The subjects prior to therapy involved [Gr. Ia - Gr. IVa] and post therapeutically [Gr. Ib - Gr. IVb]

Results: Evaluated therapeutic outcome identified significant variation in perturbed biochemical parameters assessed prior to therapy. These included alterations in serum levels of cotinine, protein C, protein S. thrombin -antithrombin complex, thrombomodulin, sialic acid, c-reactive protein, interleukin 6, p-selectin, vitamin E in LDL, vitamin C, hepatocyte growth factor, lipoprotein lipase, lipoprotein a, lipid peroxidation product, asymmetric dimethylarginine [ADMA]

Conclusion: Beneficial outcome was attained by combined multi-disciplinary therapeutic strategy alleviating variable stress-induced factors perpetuating chronic fatigue in subjects with hepatic disposition induced by environmental factors

Recommendations: Environmental factors including cigarette smoking and viral hepatitis [HEV and/or HBV co-infection] imposed in subjects with schistosomal fibrosis stress-induced symptoms of fatigue which may be co-linked to hepatotoxic insult. This could be carefully targeted by combined drug therapy influencing haemostatic immune and metabolic pathways and antioxidant defense mechanisms in subjects with hepatic disposition affecting bio-energetic capacity