Diabetic neuropathy is a common complication of both type 1 and type 2 diabetes, which affects over 90% of the diabetic patients. Although pain is one of the main symptoms of diabetic neuropathy, its pathophysiological mechanisms are not yet fully known. It is widely accepted that the toxic effects of hyperglycemia play an important role in the development of this complication, but several other hypotheses have been postulated. The management of diabetic neuropathic pain consists basically in excluding other causes of painful peripheral neuropathy, improving glycemic control as a prophylactic therapy and using medications to alleviate pain. First line drugs for pain relief include anticonvulsants, such as pregabalin and gabapentin and antidepressants, especially those that act to inhibit the reuptake of serotonin and noradrenaline. In addition, there is experimental and clinical evidence that opioids can be helpful in pain control, mainly if associated with first line drugs. Other agents, including for topical application, such as capsaicin cream and lidocaine patches, have also been proposed to be useful as adjuvants in the control of diabetic neuropathic pain, but the clinical evidence is insufficient to support their use. In conclusion, a better understanding of the mechanisms underlying diabetic neuropathic pain will contribute to the search of new therapies, but also to the improvement of the guidelines to optimize pain control with the drugs currently available.

Diabetes is a chronic and progressive syndrome commonly associated with several neuropsychiatric comorbities, of which depression is the most studied. The prevalence of depression is about two or three times higher in diabetic patients compared to the general population. It is believed that the diabetes - depression relation may be bidirectional, i.e., the depression can lead to diabetes and conversely diabetes could facilitate the emergence of depression. Depression is one of the most neglected symptoms in diabetic patients and is directly linked with lowering of quality of life. The treatment of depression in these patients is still quite ineffective and in many cases treatmentrefractory. Furthermore, some of the first choice drugs used to treat the depression affect the blood glucose control, aggravating the hyperglycemic state. These issues underscore the urgency in studies searching for new pharmacological targets for the treatment of depression associated with diabetes. For this, a better understanding of the pathophysiology that relates this comorbidity becomes critical. In this respect, this review will focus on some hypotheses that have been proposed to explain the mechanisms underlying depression associated with diabetes, highlighting the treatment options currently available and their limitations. Among these hypotheses, we will point out the hyperglycemia as a primary metabolic cause of the depression development, the involvement of the dysregulation of hypothalamic pituitary-adrenal (HPA) axis and of neurotransmitter systems, specially monoaminergic system. Besides, the role of oxidative stress, neuroinflammation and cell death, especially in hippocampus and prefrontal cortex, brain areas important for the mediation and modulation of emotional behavior will also be discussed. Finally, we will bring up the influence of the epigenetic regulation with respect to neuropsychiatric disorders.

Chlorpyrifos is a pesticide, member of the organophosphate class, widely used in several countries to manage insect pests on many agricultural crops. Currently, chlorpyrifos health risks are being reevaluated due to possible adverse effects, especially on the central nervous system. The aim of this study was to investigate the possible action of this pesticide on the behaviors related to anxiety and depression of offspring rats exposed during pregnancy. Wistar rats were treated orally with chlorpyrifos (0.01, 0.1, 1 and 10mg/kg/day) on gestational days 14-20. Male offspring behavior was evaluated on post-natal days 21 and 70 by the elevated plus-maze test, open field test and forced swimming test. The results demonstrated that exposure to 0.1, 1 or 10mg/kg/day of chlorpyrifos could induce anxiogenic-like, but not depressive-like behavior at post-natal day 21, without causing fetal toxicity. This effect was reversed on post-natal day 70.

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In the acute phase of lymphoedema, patients require comprehensive decongestive therapy (CDT), which includes skin care, an exercise regimen, manual lymphatic drainage (MLD) and regular bandaging. This study was established to determine the effectiveness of a new system of bandage therapy, the 3M™ Coban™ 2 compression system. In total, 24 patients were entered into the study (12 from UK and 12 from Canada) with a variety of clinical presentations. The mean age of the groups was 57·4 years, which varied from 26 to 79 years. Body mass index (BMI) averaged 38·9 kg/m(2), with a range from 22·7 to 67·5 kg/m(2). Of the total, eight were women with arm lymphoedema, the remainder being men and women with lymphoedema of the lower limb. All were considered to be in need of CDT. After 19 days, the reduction of limb volume was measured, which indicated a mean limb volume reduction of 1210 ml (95% confidence interval, CI, 780-1641, P < 0·001). Leg affected patients experienced greater reduction than arm affected patients (1596 ml versus 438 ml), although both groups experienced significant reduction in limb volumes (both P < 0·001). Mean percentage changes in limb volume were 14·9% and 16·1% for legs and arms, respectively. The Measure Your Medical Outcome Profile questionnaire indicated significant improvement in symptoms considered important by the patient (P < 0·0001), which also led to improvements in skin quality by reducing skin thickness and firmness. The Coban 2 compression system provides good oedema reduction in both arms and legs to reduce limb volume and improvements in symptoms associated with lymphoedema.