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41.
The adipokine, leptin, regulates blood glucose and the insulin secretory function of beta cells, while also modulating immune cell function. We hypothesized that the dual effects of leptin may prevent or suppress the autoreactive destruction of beta cells in a virally induced rodent model of type 1 diabetes. Nearly 100% of weanling BBDR rats treated with the combination of an innate immune system activator, polyinosinic:polycytidylic acid (pIC), and Kilham rat virus (KRV) become diabetic within a predictable time frame. We utilized this model to test the efficacy of leptin in preventing diabetes onset, remitting new onset disease, and preventing autoimmune recurrence in diabetic rats transplanted with syngeneic islet grafts. High doses of leptin delivered via an adenovirus vector (AdLeptin) or alzet pump prevented diabetes in>90% of rats treated with pIC+KRV. The serum hyperleptinemia generated by this treatment was associated with decreased body weight, decreased non-fasting serum insulin levels, and lack of islet insulitis in leptin-treated rats. In new onset diabetics, hyperleptinemia prevented rapid weight loss and diabetic ketoacidosis, and temporarily restored euglycemia. Leptin treatment also prolonged the survival of syngeneic islets transplanted into diabetic BBDR rats. In diverse therapeutic settings, we found leptin treatment to have significant beneficial effects in modulating virally induced diabetes. These findings merit further evaluation of leptin as a potential adjunct therapeutic agent for treatment of human type 1 diabetes.  相似文献   
42.
Residual high-on treatment platelet reactivity (HRPR) has been associated with a 2–9 fold increased risk of acute ischemic events in patients with acute coronary syndromes or coronary stenting. However, the mechanism of suboptimal platelet inhibition are still poorly understood. Aim of present study was to evaluate the role of the percentage of reticulated platelets on HRPR with ticagrelor. In patients treated with ASA (100–160 mg) and ticagrelor (90 mg twice a day) platelet reactivity and the reticulated platelets fraction (immature platelets fraction, IPF) were assessed at 30–90 days after acute coronary syndrome. Aggregation was assessed by multiple-electrode aggregometry. HRPR was defined as ADP test >417 AU*min. Our population is represented by 190 patients, divided according to tertiles values of IPF (<2.5; 2.5–3.99; ≥4 %). Higher IPF was associated to a larger platelet volume and lower platelets count (p < 0.001), and inversely related with a history of previous coronary revascularization (p = 0.03). Twenty-one out of 190 (11.0 %) patients displayed HRPR. No difference in the levels of circulating IPF was found in patients with or without HRPR (p = 0.25), with no correlation between the rate of reticulated platelets and platelet reactivity at ADP test (r = ?0.084, p = 0.26). In fact no association was observed between high levels of IPF and the occurrence of HRPR (adjusted OR[95 % CI] = 0.69[0.34–1,37], p = 0.28), even after correction for baseline differences. In patients treated with ticagrelor, the levels of circulating reticulated platelets assessed at 30–90 days post-ACS are not associated with platelet reactivity or the occurrence of HRPR.  相似文献   
43.
Human visceral (VL, also known as Kala-azar) and cutaneous (CL) leishmaniasis are important infectious diseases affecting countries in East Africa that remain endemic in several regions of Ethiopia. The transmission and epidemiology of the disease is complicated due to the complex life cycle of the parasites and the involvement of various Leishmania spp., sand fly vectors, and reservoir animals besides human hosts. Particularly in East Africa, the role of animals as reservoirs for human VL remains unclear. Isolation of Leishmania donovani parasites from naturally infected rodents has been reported in several endemic countries; however, the status of rodents as reservoirs in Ethiopia remains unclear. Here, we demonstrated natural Leishmania infections in rodents. Animals were trapped in 41 localities of endemic and non-endemic areas in eight geographical regions of Ethiopia and DNA was isolated from spleens of 586 rodents belonging to 21 genera and 38 species. Leishmania infection was evaluated by real-time PCR of kinetoplast (k)DNA and confirmed by sequencing of the PCR products. Subsequently, parasite species identification was confirmed by PCR and DNA sequencing of the 18S ribosomal RNA internal transcribed spacer one (ITS1) gene. Out of fifty (8.2%) rodent specimens positive for Leishmania kDNA-PCR and sequencing, 10 were subsequently identified by sequencing of the ITS1 showing that five belonged to the L. donovani complex and five to L. tropica. Forty nine kDNA-positive rodents were found in the endemic localities of southern and eastern Ethiopia while only one was identified from northwestern Ethiopia. Moreover, all the ten ITS1-positive rodents were captured in areas where human leishmaniasis cases have been reported and potential sand fly vectors occur. Our findings suggest the eco-epidemiological importance of rodents in these foci of leishmaniasis and indicate that rodents are likely to play a role in the transmission of leishmaniasis in Ethiopia, possibly as reservoir hosts.  相似文献   
44.

Aims

To determine the cross-sectional threshold at which hemoglobin A1c (HbA1c) is associated with polyneuropathy in healthy controls, and the values associated with the most pronounced decline in nerve function in patients with diabetes.

Methods

We used data from a cross-sectional cohort study of healthy controls and type 2 diabetes patients assessed between November 2010 and May 2013. Healthy controls and patients with diabetes were compared at different HbA1c ranges: <5.5%, 5.5–5.9%, and 6–6.4% for controls, and 6.5–7.4% and >7.5% for patients with diabetes.

Results

The total cohort included 53 controls and 164 patients with diabetes. Subclinical small nerve fiber impairments were observed in controls at HbA1c levels of 5.5–6%, compared with HbA1c <5.5%, for example: lower Laser Doppler flare imaging area of 2.8?±?1.4 versus 3.9?±?2?mm2. The most prominent decline in both small and large nerve fiber function was seen with less impaired glycemic control and shorter duration of diabetes, i.e. at HbA1c levels of 6.5–7.4%, compared with >7.5%.

Conclusions

These findings underscore the importance of early treatment at the prediabetes and early diabetes stages to prevent nerve fiber decline that is likely irreversible.  相似文献   
45.

Aim

Neuropathy and neuropathic pain are common complications of type 1 diabetes (T1D). We aimed to determine if sex-specific differences in neuropathic pain are present in adults with longstanding T1D.

Methods

Canadians with ≥50?years of T1D (n?=?361) completed health history questionnaires that included assessment of neuropathy (defined by Michigan Neuropathy Screening Instrument questionnaire components ≥3; NEUROPATHYMNSI-Q) and neuropathic pain. Multivariable logistic regression was used to determine sex-differences in neuropathic pain controlling for neuropathy.

Results

Participants had mean age 66?±?9?years, median diabetes duration 53[51,58] years, mean HbA1c 7.5?±?1.0%, and 207(57%) were female. Neuropathic pain was present in 128(36%) of all participants, more prevalent among those with NEUROPATHYMNSI-Q compared to those without [96(63%) vs. 31(15%), p?<?0.001], and more prevalent in females compared to males [87(42%) vs. 41(27%), p?=?0.003]. Independent of the presence of NEUROPATHYMNSI-Q and other factors, female sex was associated with the presence of neuropathic pain [OR 2.68 (95% CI 1.4–5.0), p?=?0.002].

Conclusions

We demonstrated a novel sex-specific difference in neuropathic pain in females compared to males with longstanding T1D, independent of the presence of neuropathy. Further research using more objective measures of neuropathy than the MNSI is justified to further understand this sex-specific difference.  相似文献   
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