Incretin-based therapy for glycemic control of hospitalized patients with type 2 diabetes: a systematic review.

Incretin-based therapy leads to glycemic control in a glucose-dependent manner with a low risk of hypoglycemia, making it appealing for use in the hospital. The aim of this systematic review was to assess the benefits of incretin-based therapy in patients with type 2 diabetes hospitalized outside of the intensive care unit. We searched for studies published up to August 2021 in the PubMed and Scopus databases. Clinical trials comparing incretin-based therapy (alone or in combination with insulin) versus an insulin regimen were selected. The results of the included studies showed that incretin-based therapy showed mean blood glucose values, a percentage of records within the therapeutic target, and a percentage of treatment failure similar to insulin management, particularly in patients with mild to moderate hyperglycemia. Furthermore, incretin-based treatment was associated with a lower total insulin dose and a lower incidence of hypoglycemia. In conclusion, incretin-based therapy achieved glycemic control similar to insulin treatment in patients with type 2 diabetes hospitalized outside the intensive care unit and has the advantages of reducing the insulin requirement and a lower risk of hypoglycemia.

Impact on beef cattle productivity of infection with anthelmintic-resistant nematodes.

ABSTRACTAims: The main goal of the current study was to evaluate, on a commercial beef cattle farm, the impact of infection with gastrointestinal nematodes resistant to both ivermectin (IVM) and moxidectin (MXD) on the productivity of calves.Methods: Male Aberdeen Angus calves, aged 9-11 months, with faecal nematode egg counts (FEC) ≥200 epg and body weight ≥190 kg, were allocated to two herds. Herd A (n = 90) grazed a maize-winter forage crop rotation and Herd B (n = 90) grazed a 2-year-old Agropyrum pasture. On Day 0 in each herd, calves were randomly allocated into five groups (n = 18), which were treated with 0.2 mg/kg IVM; 0.2 mg/kg MXD; 3.75 mg/kg ricobendazole (RBZ), both IVM and RBZ, or remained untreated. Faecal samples collected on Days -1 and 19 were used to determine the percentage reduction in FEC, and genera of the nematodes were determined by the identification of the third-stage larvae recovered from faecal cultures. Total weight gain was determined from body weights recorded on Days -1 and 91.Results: Overall mean reduction in FEC was 42% for IVM, 67% for MXD, 97% for RBZ and 99% for IVM + RBZ. The reduction in FEC for Cooperia spp. was ≤78% for IVM and MXD, and for Haemonchus spp. was 0 and 36% for IVM and MXD, respectively, confirming the presence of parasites resistant to both anthelmintics. Only IVM + RBZ treatment resulted in 100% efficacy against Haemonchus spp. The overall estimated mean total weight gain for calves treated with IVM was 15.7 (95% CI = 11.9-19.7) kg and for calves treated with IVM + RBZ was 28.8 (95% CI = 25-32.5) kg (p < 0.001). Mean total weight gain for calves treated with MXD was 23.5 (95% CI = 19.7-27.2) kg.Conclusions and clinical relevance: In calves naturally infected with resistant nematodes, under the production system assessed here, weight gains were lower in calves treated with anthelmintics that were moderately or highly ineffective compared to those treated with highly effective anthelmintics. These results demonstrate to farmers and veterinarians the importance of a sustainable and effective nematode control under field conditions.

Utility of neutrophil-to-lymphocyte ratio plus C-reactive protein for infection in systemic lupus erythematosus.

OBJECTIVE: To analyze the utility of neutrophil-to-lymphocyte ratio (NLR) plus C-reactive protein (CRP) to differentiate between infection and active disease in patients with SLE. METHODS: A cross-sectional study of a cohort of patients with SLE was carried out. Blood samples from four groups (patients without infection or active disease, patients with infection, patients with active disease, and patients with both infection and active disease) before therapeutic interventions were analyzed. We excluded patients with current malignancy, pregnancy, ischemic heart disease or use of antimicrobials during previous 7 days. Hematological cell count, CRP and cultures were obtained. We constructed receiver operating characteristic curves; sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated. RESULTS: Forty patients were included. NLR cut-off ≥6.3 had sensitivity 70%, specificity 85%, PPV 83% and NPV 74% to detect patients with non-viral infections. A CRP cut-off ≥7.5 mg/L had sensitivity 90%, specificity 75%, PPV 78% and NPV 88% to detect infections regardless of SLE activity. Combination of CRP plus NLR improves the specificity to 90% and PPV to 88%. Excluding the group with both infection and active disease, CRP plus NLR expands specificity to 95% and NPV to 90%. CONCLUSION: In our experience, levels of CRP, particularly CRP plus NLR, were useful in differentiating patients with SLE from those with suspected non-viral infection regardless of the activity of the disease.

Pharmaco-parasitological evaluation of the ricobendazole plus levamisole nematodicidal combination in cattle.

The goals of the current study were to evaluate the potential pharmacokinetic (PK) interactions and the clinical efficacy occurring after the subcutaneous (s.c.) administration of ricobendazole (RBZ) and levamisole (LEV) given both separately and co-administered to calves naturally infected with susceptible gastrointestinal nematodes. The clinical efficacy was shown in two seasons, winter and spring, with predominance of different nematode populations. Groups of 15 calves were treated with RBZ alone, LEV alone and RBZ + LEV combination, and an untreated group was kept as a Control. RBZ and LEV plasma concentrations were quantified by HPLC. The clinical efficacy was determined by the faecal egg count reduction test. RBZ and LEV have similar plasma persistence, being detected in plasma over 24 hr post-treatment. No PK interactions were observed after the combined treatment, with similar PK parameters (p > .05) obtained for the single-drug and the combination-based strategy. In winter, the observed clinical efficacies were 96%, 99% and 100% for groups treated with RBZ, LEV and RBZ + LEV, respectively; however, in spring, the efficacies were 95%, 93% and 96% for the same groups. Remarkably, the combination was the only treatment that achieved 100% clinical efficacy against both Haemonchus spp and Ostertagia spp in winter; but the increased presence of Ostertagia spp. in spring (28% in untreated group) determined a tendency to reduced efficacies compared to winter time (only 10% of Ostertagia spp. in untreated group), even for the combined treatment. Overall, in a scenario where the nematode population is susceptible, the RBZ + LEV treatment may be a valid combination in cattle to delay the development of resistance, especially in winter when this combination achieved 100% of efficacy. Thus, selection of anthelmintic resistance will never occur. In fact, this is one of the greatest challenges for the whole cattle production system: to be one step ahead of anthelmintic resistance.

Effect of ezetimibe plus pravastatin on endothelial dysfunction in patients with systemic lupus erythematosus.

BACKGROUND: Patients with systemic lupus erythematosus (SLE) have a higher risk for cardiovascular disease (CVD), not fully explained by the conventional risk factors. These patients have endothelial dysfunction (ED) as an early process of atherosclerosis, which can be reversed with therapy. OBJECTIVE: To determine the effect of ezetimibe plus pravastatin on endothelial function in patients with SLE after 12 months of treatment. PATIENTS AND METHODS: An open study, before and after, which assessed the effect of ezetimibe plus pravastatin treatment, was performed. Twenty two patients (21 women and one man) with diagnosis of SLE were studied, with a mean age 40 ± 5 years. Endothelial dysfunction was evaluated using vascular ultrasound of the brachial artery in order to measure the flow-mediated vasodilation (FMV) basal and after 12 months of treatment with pravastatin 40 mg/day plus ezetimibe 10 mg/day. In addition, a lipid profile: total cholesterol (TC), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), and serum C-reactive protein (CRP), was done. RESULTS: We found a basal FMV of 7.58% and 18.22% after 12 months of treatment, with an improvement of 10.64 points 95% CI (7.58-13.58), p < 0.001. TC decreased from 201.3 ± 58.9 mg/dL to 158.06 ± 50.13 mg/dL (p < 0.01); LDL-C from 125.78 ± 44.4 mg/dL to 78.8 ± 32.9 mg/dL (p < 0.001); HDL-C increased from 49.0 ± 16.8 mg/dL to 52.2 ± 13.8 mg/dL (p = 0.077). The basal and final concentrations of CRP were 4.49 and 2.8, respectively, with a mean decrease of 2.11 mg/dL, 95% CI (0.908-3.32), p < 0.002. Both drugs were well tolerated. CONCLUSION: Ezetimibe plus pravastatin significantly improved FMV in patients with SLE, decreasing ED and the lipid profile. This treatment ameliorated an early process of atherosclerosis and a risk factor for CVD.

Oxidative stress in Mexicans with diffuse cutaneous systemic sclerosis.

To compare oxidative stress (OS) biomarkers and antioxidant capacity of plasma (ACP) between dcSSc (diffuse cutaneous systemic sclerosis) and healthy Mexicans and their possible relationship with autoantibodies, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and uric acid (UA). We included 28 dcSSc and 28 healthy individuals. Patients were grouped in early and late dcSSc and were excluded if they had infections, neoplasias, comorbidity, or antioxidant treatment. Lipoperoxidation products (malondialdehyde), protein oxidation products (carbonyls, dityrosines), ACP, CRP, ESR, and UA were investigated. Age was 47.5 ± 10 in dcSSc versus 48 ± 7 years in controls. In dcSSc, OS was higher and ACP was decreased versus controls (p < 0.001). OS was similar in early and late dcSSc. Anti-Scl-70 (anti-topoisomerase I) was associated with a higher OS (p < 0.05). Eight dcSSc patients had hyperuricemia (28.5 %). A significant correlation between UA and malondialdehyde, dityrosines and carbonyls levels (r = 0.52, r = 0.78 and r = 0.69, p < 0.01) respectively, was found in dcSSc group. A high level of ESR was present in 71 % and CRP in 40 % of dcSSc patients. Mexican dcSSc patients had elevated lipid/protein OS with respect to healthy controls. These OS biomarkers have direct correlation with UA levels. ESR and CRP were elevated in a great number of dcSSc patients. These biochemical markers suggest that dcSSc patients have a continuous stimulus for endothelial dysfunction and accelerated atherogenesis.

Seasonal variations in the composition of ram seminal plasma and its effect on frozen-thawed ram sperm.

It has been proposed that seminal plasma (SP) in the extender or in post-thaw media can prevent and revert cold-shock damage in cryopreserved ram sperm; however, this was dependent on season. We evaluated sperm parameters from Frisian ram semen incubated for various intervals with SP from all seasons and stored at -18 or -196 degrees C. At both temperatures, SP from autumn or winter increased (P<0.05) sperm motility, whereas no SP, or SP from spring or summer, had no effect. However, neither viability nor membrane or acrosomal status were modified by SP. Thirteen SP proteins were bound to the sperm surface (16.1, 16.7, 17.4, 23.3, 25.2, 27.5, 35.0, 40.0, 49.0, 53.5, 55.5, 61.0, and 86.0kDa). The SP proteins that bound to sperm were affected by season, but not by conservation temperature. Sperm incubated with SP from autumn had increased concentrations of five proteins; two were identified (with specific antibodies) as RSVP14 and RSVP20. In conclusion, SP from autumn and winter improved sperm motility of frozen-thawed ram sperm, and storage of ram SP at -18 or -196 degrees C did not affect protein composition. The SP proteins that bound to the sperm surface may be responsible for sperm membrane stabilization and should be further investigated.

Evidence of alpha1-adrenoceptor functional changes in omental arteries of patients with end-stage renal disease.

1 Alpha1-Adrenoceptor (alpha1-AR) subtypes were characterized in isolated omental arteries obtained after abdominal surgery in patients with end-stage renal disease (ESRD) or with Diabetes Mellitus type 2 plus ESRD (ESRD-DM). 2 Omental arteries from patients with ESRD and ESRD-DM elicited a significant increase in sensitivity to phenylephrine with a pD(2) (-log EC50) of 6.7 and 6.6, respectively, vs. the control (5.8, P < 0.001). 3 Stimulation with phenylephrine was conducted in the presence or absence of selective alpha1-AR competitive antagonists: 5-methylurapidil (alpha1A-), AH11110A (1-[biphenyl-2-yloxy]-4-imino-4-piperidin-1-yl-butan-2-ol; alpha1B-) and BMY7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro [4.5] decane-7,9-dione; alpha(1D)-). The relative abundance of mRNA for all three alpha(1)-ARs was determined. 4 The maximal contractile responses to phenylephrine were: E(max) 1.59 +/- 0.17, 1.48 +/- 0.08 and 1.55 +/- 0.14 g for the ESRD, ESRD-DM and control groups, respectively. 5 Functionally, there was an increment in the affinity for the alpha(1A)-AR antagonist (pA2: control 7.45, ESRD 8.36, ESRD-DM 8.0; P < 0.01), and a reduction in the alpha1B-AR antagonist affinity (8.3 for controls, 7.6 for ESRD and 7.3 for ESRD-DM; P < 0.01) associated with renal disease. The affinities for the alpha1D-AR antagonist were similar among the studied groups (8.5 for the controls, 8.7 for the ESRD and 8.1 for the ESRD-DM groups). 6 Renal disease increased mRNA expression of alpha(1B)-ARs and reduced both alpha1A- and alpha(1D)-ARs subtypes in ESRD and ESRD-DM patients. 7 The results suggest that human omental arteries exposed to chronic uraemia show vascular hypersensitivity to phenylephrine, because of functional alpha1-AR changes.

Percutaneous radiofrequency ablation: relationship between different probe types and procedure time on length and extent of osteonecrosis in dog long bones.

PURPOSE: We have been using radiofrequency ablation for the percutaneous treatment of osteoid osteoma since 2001. Frequently, lesions are located near the joint surface, involve the vertebral body or are close to major nerves. We seek to determine whether radiofrequency ablation (RFA) can be used safely in these cases. MATERIALS AND METHODS: A total of 65 lesions were induced in 4 dogs. Each dog underwent RFA on the diaphysis of long bones, as well as femoral and humeral heads. Four different sessions were carried out by using 1- and 2-cm probes with or without a cool-tip system and by varying the timing of the procedure. Plain film, CT, and MRI were obtained. All bone samples were examined histologically. RESULTS: The dogs' activity after the procedure was normal. No pathologic fractures occurred despite unrestricted activity of the animals. Cortical bone was always respected; therefore, articular cartilage has not been damaged. Radiological findings were characteristic. There were no significant differences in lesion size, probe type, and the duration of the procedure. The mean lesion diameter perpendicular to the electrode was 18.5 mm. CONCLUSIONS: Our study confirms the insulative effect of cortical bone. RFA can be safely performed close to the joint surface without damaging the cartilage.

Bilateral parotid cysts as presentation of Sjögren's syndrome.

We present a case of a 40-year woman with bilateral parotid salivary gland enlargement as presentation of primary Sjögren's syndrome. Computed tomography (CT) and magnetic resonance imaging (MRI) showed parotid cysts, suggestive of cystic benign lymphoepithelial lesions. A sub-labial biopsy confirmed the syndrome. After 24-month follow-up, the left parotid cysts remain the same, whereas other cysts have appeared in the right parotid gland. Parotid involvement in Sjögren's syndrome is discussed.

Pleomorphic adenoma of the breast. Case report.

A clinicopathologic study of a pleomorphic adenoma of the breast is presented and attention is drawn to a previously unreported association with a cyst. Malignancy was strongly suspected in the light of radiologic features. Immunohistochemistry stresses the similarity between pleomorphic adenoma of salivary gland and breast. A common histogenesis of the two entities is also suggested. Ontogenetic links of both glands are mentioned.