Diabetes mellitus and electrolyte disorders

Diabetic patients frequently develop a constellation of electrolyte disorders. These disturbances are particularly common in decompensated diabetics, especially in the context of diabetic ketoacidosis or nonketotic hyperglycemic hyperosmolar syndrome. These patients are markedly potassium-, magnesium- and phosphate-depleted. Diabetes mellitus (DM) is linked to both hypo- and hyper-natremia reflecting the coexistence of hyperglycemia-related mechanisms, which tend to change serum sodium to opposite directions. The most important causal factor of chronic hyperkalemia in diabetic individuals is the syndrome of hyporeninemic hypoaldosteronism. Impaired renal function, potassium-sparing drugs, hypertonicity and insulin deficiency are also involved in the development of hyperkalemia. This article provides an overview of the electrolyte disturbances occurring in DM and describes the underlying mechanisms. This insight should pave the way for pathophysiology-directed therapy, thus contributing to the avoidance of the several deleterious effects associated with electrolyte disorders and their treatment.     

Comparative mortality ratios of cancer among men in Greece across broad occupational groups

Aim

The purpose of this study was to compare site-specific cancer death rates in male workforce across major occupational groups in Greece.

Methods

Data on cancer mortality in men aged 25?C69?years during the period 2000?C2005 were obtained from National Statistical Service of Greece. Age- and site (ICD-10)-specific cancer death rates and the ratio of standardized cancer death rates (i.e. the comparative mortality ratio and 95% confidence interval) across seven major occupational groups (ISCO-88) were calculated.

Results

The proportion of total deaths due to cancer was ranged between 6.6, 24.3, 37.4, and 39.4% for the age groups of 15?C39, 40?C49, 50?C59, and 60?C69?years, respectively. Respiratory and gastrointestinal malignancies constituted 70% of the total cancer mortality in our population. Groups of elementary occupations, skilled agricultural workers, and plant workers showed very high mortality ratios of respiratory cancer while low ratios were found for the groups of professionals, legislators, senior officials, and managers and paradoxically for craft and related workers. Compared to the other groups, skilled agricultural and elementary groups showed higher rates of gastrointestinal and other or no determined malignancies in the age groups of 40?C49 and 50?C59?years old. Plant workers and machine operators/assemblers exhibited high mortality rates for most cancer sites especially in the elders group (60?C69?years) and a mortality ratio of genitourinary cancer that differed significantly compared to any other group.

Conclusions

Up to 3.5-fold variations were found in site-specific cancer mortality ratios among men in Greece across broad occupational groups. The extent of the variation attributed to specific socioeconomic and/or occupational factors could not be estimated in the current study but the observed differences might stimulate thinking and preventive actions as well as point to potential hypotheses to pursue using research methods in which job and life related factors should be directly measured and controlled.     

Anticancer and cytotoxic effects of a triorganotin compound with 2-mercapto-nicotinic acid in malignant cell lines and tumor bearing Wistar rats

Nowadays, investigation for possible therapeutic applications of various metal-based drugs attracts the scientific interest worldwide. The triorganotin compound bis[triphenyltin(IV)](3-carboxy-pyridine-2-thionato) (SnMNA), was tested for its anti-proliferative and antitumor activities. Cytotoxic activity was assessed by Trypan blue and 3-(4.5-dimethylthiazol-2-yl)-2.5-diphenyltetrazolium bromide assay (MTT). SnMNA exhibited potent cytotoxic effects against leiomyosarcoma cells (LMS) and human breast adenocarcinoma cells (MCF-7), which is 200 times stronger than that of cisplatin. Moreover, SnMNA induced significant apoptosis in LMS and MCF-7 cells characterized by flow cytometry analysis and DNA fragmentation. Acute and chronic toxicity studies on Wistar rats caused kidney and lung toxicity at a single dose of 80 mg/kg Body Weight (BW) or four repeated doses of 8 mg/kg BW once per week. Furthermore, antitumor activity studies on sarcoma bearing Wistar rats revealed that SnMNA complex at four repeated doses of 5.4 mg/kg BW every three days prolonged mean survival time of the animal at 200% and decreased mean tumor growth rate (MTGR) compared to the control group (p < 0.05). It is noteworthy to mention that the 30% (3 out of 10) of the bearing animals were totally cured. These findings indicate that SnMNA might be a promising new antitumor agent.     

Translocation t(12;13)(p13;q14) in a patient with imatinib-sensitive MDS/MPD associated with resistance to treatment: review of the literature

The category of myelodysplastic syndromes/myeloproliferative diseases (MDS/MPD) is a relatively new group of malignant hematologic diseases developed by the World Health Organization. These hematologic disorders lack the BCR/ABL fusion gene, although they can be associated with chromosomal translocations that involve genes encoding other protein kinases. Imatinib mesylate was recognized as a potent inhibitor of some of those kinases. We present a patient with a previously treated acute myeloid leukemia, who, after a 9-year-long remission, developed an MDS/MPD with normal karyotype, which initially responded to imatinib mesylate. Translocation t(12;13)(p12;q14) was detected after loss of response to imatinib treatment. Translocation t(12;13) is rare. It has been described in several hematologic malignancies including chronic myelomonocytic leukemia but not in MDS/MPD, previously described as Philadelphia-negative chronic myelogenous leukemia. Moreover, the correlation of this molecular abnormality with loss of efficacy of imatinib is unique in the literature.     

Emerging drugs for Waldenström's macroglobulinemia

INTRODUCTION: Waldenstr?m's macroglobulinemia (WM) is a rare but distinct B-cell lymphoproliferative disorder characterized by lymphoplasmacytic bone marrow infiltration and IgM monoclonal paraproteinemia. Alkylators or nucleosides analogs, often in combination with rituximab, are the most commonly used drugs, but WM will relapse and even salvage treatments may fail. AREAS COVERED: We present recent advances on the treatment of WM, focusing on drugs that are under clinical investigation and for which data indicate promising activity and positive future prospects. Bortezomib is a proteasome inhibitor that eventually becomes a major treatment option for WM. Everolimus and perifosine which target mTOR (mammalian target of rapamycin) and Akt, respectively, of the PI3K/AKT/mTOR pathway showed some activity. Bendamustine, a novel alkylating agent is active, especially in combination with rituximab. Immunomodulatory drugs can act synergistically with rituximab but are toxic. Targeting surface antigens of the lymphoplasmatic cells have shown promising results. EXPERT OPINION: Combinations of novel drugs with established agents are feasible and increase response rates but whether there will be an increase in the survival of patients with WM needs further investigation. The toxicity profile is an important determinant for the feasibility of these drugs in patients with WM.     

What restricts the clinical use of nicotinic acid?

Nicotinic acid is the oldest hypolipidemic agent in use, since 1955. It possesses broad-spectrum lipidmodifying properties including reduction of total cholesterol, low density lipoprotein (LDL) cholesterol and triglycerides. In addition, nicotinic acid is the most potent available hypolipidemic agent for increasing plasma high density lipoprotein (HDL) cholesterol and decreasing lipoprotein (a) levels. Clinical trials have demonstrated that nicotinic acid can decrease cardiovascular morbidity and mortality. However, nicotinic acid is underused in the clinical setting due to its high rate of side effects, including flushing, gastrointestinal disorders, rash, hyperglycemia and hyperuricemia. The nicotinic acid-associated side effects and their management are the focus of this review.     

Prediabetes: to treat or not to treat?

The incidence of diabetes is continuously increasing worldwide. Pre-diabetes (defined as impaired glucose tolerance, impaired fasting glucose or both) represents an intermediate state, which often progresses to overt diabetes within a few years. In addition, pre-diabetes may be associated with increased risk of microvascular and macrovascular complications. Thus, reverting a pre-diabetic state as well as preventing the development of diabetes represents enormous challenge for the clinician. Lifestyle modification in pre-diabetic individuals was found particularly effective in the prevention of diabetes. However, compliance to lifestyle modification measures can be a crucial problem in the everyday clinical practice, especially in developing countries. During the last decade many studies support the use of anti-diabetic treatment schemes in pre-diabetic subjects to be advantageous. The American Diabetes Prevention Program (DPP) as well as other minor studies and meta-analyses has convincingly demonstrated the efficacy of metformin in this patient group. In addition, results of the 10 year DPP follow up have recently been published, demonstrating the long term safety and sustainability of metformin treatment benefits in this population. In contrast to metformin, the evidence from the use of other anti-diabetic agents (thiazolidinediones, a-glucosidase inhibitors, incretin mimetics) in pre-diabetic individuals is rather inadequate and prospective data is further needed. Furthermore, large scale studies with hard clinical endpoints are needed to delineate the effect of pre-diabetes treatment on macro- and microvascular complications. In conclusion, several strategies of patient management, mainly lifestyle modification and pharmacological interventions can prevent diabetes development in subjects diagnosed with pre-diabetes or even revert pre-diabetic state. However, whether this biochemical improvement can be translated into actual clinical benefit remains to be established.