Obstructive sleep apnea and diabetic neuropathy: a novel association in patients with type 2 diabetes

Rationale: Diabetic peripheral neuropathy is common and causes significant morbidity. Obstructive sleep apnea (OSA) is also common in patients with type 2 diabetes. Because OSA is associated with inflammation and oxidative stress, we hypothesized that OSA is associated with peripheral neuropathy in type 2 diabetes. Objectives: To assess the relationship between OSA and peripheral neuropathy in patients with type 2 diabetes. Methods: A cross-sectional study of adults with type 2 diabetes recruited randomly from the diabetes clinic of two UK hospitals. Measurements and Main Results: Peripheral neuropathy was diagnosed using the Michigan Neuropathy Screening Instrument. OSA (apnea-hypopnea index ≥ 5 events/h) was assessed using home-based, multichannel respiratory monitoring. Serum nitrotyrosine was measured by ELISA, lipid peroxide by spectrophotometer, and microvascular function by laser speckle contrast imaging. Two hundred thirty-four patients (mean [SD] age, 57 [12] yr) were analyzed. OSA prevalence was 65% (median apnea-hypopnea index, 7.2; range, 0-93), 40% of which were moderate to severe. Neuropathy prevalence was higher in patients with OSA than those without (60% vs. 27%, P < 0.001). After adjustment for possible confounders, OSA remained independently associated with diabetic neuropathy (odds ratio, 2.82; 95% confidence interval, 1.44-5.52; P = 0.0034). Nitrotyrosine and lipid peroxide levels (n = 102, 74 with OSA) were higher in OSA and correlated with hypoxemia severity. Cutaneous microvascular function (n = 71, 47 with OSA) was impaired in OSA. Conclusions: We describe a novel independent association between diabetic peripheral neuropathy and OSA. We identified increased nitrosative/oxidative stress and impaired microvascular regulation as potential mechanisms. Prospective and interventional studies are needed to assess the impact of OSA and its treatment on peripheral neuropathy development and progression in patients with type 2 diabetes.     

Investigation of antioxidant and anti-nociceptive potential of isoxazolone,pyrazolone derivatives,and their molecular docking studies

A series of new isoxazolone ( 3a – d ) and pyrazolone ( 4a – d ) derivatives were synthesized and assessed for their antioxidant and analgesic activity. Among synthesized compounds, 3b and 4b having nitro (NO₂) group show high analgesic activity at a dose of 6 mg/kg. Analgesic activity was further proceeded to explore the contribution of opioidergic mechanisms in the mediation of analgesic effects. Animals were administered with naloxone, a nonselective opioid inverse agonist, at the dose of 0.5 mg/kg. The results obtained suggested that the analgesic effects of the synthesized compounds were not reversed by naloxone, specifying that the compounds 3b and 4b do not follow the opioidergic pathway in order to relieve pain in animal models. Further, the binding interactions of compounds 3b and 4b were analyzed by docking them against nonopioid receptors COX-1 (3N8X) and COX-2 (3LN1). The results demonstrate the analgesic potential of isoxazolone and pyrazolone derivatives, especially compounds 3b and 4b can be considered promising lead molecules for further investigation and development into potent analgesic drugs. In addition, the antioxidant potential of compounds was also found to be related to better analgesic activity, thus providing an insight into the role of oxidative stress in the mediation of analgesia.     

A platinum blue complex exerts its cytotoxic activity via DNA damage and induces apoptosis in cancer cells

Here, we describe the characteristics of a Pt‐blue complex [Pt₄(2‐atp)₈(H₂O)(OH)] (2‐atp: 2‐aminothiophenol) as a prodrug for its DNA‐binding properties and its use in cancer therapy. The nature of the interaction between the Pt‐blue complex and DNA was evaluated based on spectroscopic measurements, the electronic absorption spectra, thermal behavior, viscosity, fluorometric titration, and agarose gel electrophoresis. Our results suggested that the compound was able to partially intercalate DNA and appeared to induce both single‐ and double‐stranded breaks (DBS) on DNA in vitro, but no DSBs in cells. The ability of the compound to induce DNA damage was dependent on reactive oxygen species (ROS) in vitro. There was also elevated formation of ROS and SOD expression in response to drug treatment in cell culture. The complex was found to be more cytotoxic to cancer cells in comparison with noncancer controls using WST‐1 assay. The mean of cell death was determined to be apoptosis as assessed via biochemical, morphological, and molecular observations, including DNA condensation/fragmentation analysis, live cell imaging microscopy, TUNEL analyses, and increase in the levels of pro‐apoptotic genes such as Bag3, Bak, Bik, Bmf, and Hrk. Hence, the Pt‐blue complex under study grants premise for further studies.     

Retrospective Detection and Complete Genomic Sequencing of Canine morbillivirus in Eurasian Otter (Lutra lutra) Using Nanopore Technology

The Eurasian otter (Lutra lutra) is a piscivorous apex predator in aquatic habitats, and a flagship species of conservation biology throughout Europe. Despite the wide distribution and ecological relevance of the species, there is a considerable lack of knowledge regarding its virological and veterinary health context, especially in Central Europe. Canine morbillivirus (Canine distemper virus (CDV)) is a highly contagious viral agent of the family Paramyxoviridae with high epizootic potential and veterinary health impact. CDV is present worldwide among a wide range of animals; wild carnivores are at particular risk. As part of a retrospective study, lung-tissue samples (n = 339) from Eurasian otters were collected between 2000 and 2021 throughout Hungary. The samples were screened for CDV using a real-time RT-PCR method. Two specimens proved positive for CDV RNA. In one sample, the complete viral genome was sequenced using a novel, pan-genotype CDV-specific amplicon-based sequencing method with Oxford Nanopore sequencing technology. Both viral sequences were grouped to a European lineage based on the hemagglutinin-gene phylogenetic classification. In this article, we present the feasibility of road-killed animal samples for understanding the long-term dynamics of CDV among wildlife and provide novel virological sequence data to better understand CDV circulation and evolution.     

In vitro sensitivity of Blastocystis hominis to garlic, ginger, white cumin, and black pepper used in diet

To determine the growth pattern and in vitro susceptibility of Blastocystis hominis to metronidazole (MTZ), garlic, ginger, white cumin, and black pepper. Stool specimens were collected from 16 irritable bowel syndrome (IBS) and 10 controls between July–November 2010. Stool microscopy and culture for B. hominis was performed. Drug susceptibility assays was done using 0.01 and 0.1 mg/ml of MTZ, garlic, ginger, white cumin, and black pepper. Effect was assessed on B. hominis culture after 48 h. Stool DNA was extracted using stool DNA extraction kit (Qiagen) and polymerase chain reaction (PCR) done using subtype-specific sequence-tagged-site primers. B. hominis genotype 3 and coinfection of 1 and 3 tended to grow well in culture compared to isolated type 1 infection. Exposed to MTZ at a concentration of 0.01 mg/ml, 38% (6/16) B. hominis from IBS did not grow in culture compared to 100% (10/10) of B. hominis from control (p = 0.001). When they were exposed to MTZ at 0.1 mg/ml, 56% (9/16) B. hominis from IBS did not grow in cultures compared to 100% (10/10) from control (p = 0.01). Forty-four percent (7/16) B. hominis from IBS did not grow in culture compared to 100% (10/10) B. hominis from control when exposed to garlic at a concentration of 0.01 mg/ml (p = 0.003) and following exposure to garlic at 0.1 mg/ml, 38% (6/16) B. hominis from IBS did not grow in cultures compared to 100% (10/10) from control (p = 0.001). B. hominis isolates from IBS had a cell count of 6,625 at a MTZ concentration of 0.01 mg/ml that reduced to 1,250 as MTZ concentration was increased to 0.1 mg/ml (p = 0.08). B. hominis from IBS with a mean cell count of 3 × 10⁵ at baseline decreased to 1 × 10⁴ when exposed to garlic at 0.01 mg/ml (p < 0.001) and to 1 × 10³ (p < 0.001) when garlic was 0.1 mg/ml. B. hominis from IBS cell count decreased to 1 × 10⁵ when exposed to white cumin at 0.01 mg/ml (p = 0.01) and to 1 × 10⁵ (p < 0.001) when white cumin was 0.1 mg/ml. Exposed to black pepper at 0.1 mg/ml, cell count of B. hominis from IBS decreased to 1 × 10⁵ (p = 0.01). B. hominis from IBS decreased to 1.3 × 10⁵ exposed to ginger at 0.01 mg/ml (p = 0.001). B. hominis isolates were mostly genotypes 3, type 1 and 3 coinfection, and non-typeable B. hominis isolates. B. hominis isolates from IBS mostly genotype 1 demonstrated an increased sensitivity to garlic at 0.01 mg/ml with a B. hominis cell count of 3,714 compared to 6,142 when exposed to 0.01 mg/ml of MTZ. However, this sensitivity did not increase as garlic concentration was increased to 0.1 mg/ml, for B. hominis cell count was 6,000 compared to 1,428 as MTZ was increased to 0.1 mg/ml.     

Takayasu arteritis in children

Takayasu arteritis (TA) is a large vessel vasculitis that usually affects young female patients during the second and third decades of life, but has been reported in children as young as 24 months of age. Aim of this report was to describe four children (two girls) with TA, as well as summarizing main published studies. The mean age at presentation of our cases was 11 years (range 8–15). Three patients were Caucasians and one Asian. Arterial hypertension was the commonest mode of presentation followed by systemic symptoms. Other related symptoms were due to ischemia and consisted of abdomen, chest, and limb pain. An abdominal bruit was noted in only one patient. Inflammation markers were always abnormal. Angiography was performed in all cases; left subclavian artery and common carotid artery were more frequently involved. Renal artery stenosis was observed in two patients. One boy was diagnosed as having an associated immune deficiency (Wiskott-Aldrich syndrome). Treatment modalities included prednisone (n = 4), methotrexate (n = 3), and mycophenolate mofetil (MMF) (n = 1). Surgery was required in two patients. Follow-up ranged from 3 to 10 years since diagnosis. In three cases antihypertensive drugs and methotrexate were stopped, and prednisone was reduced to 7.5 mg/day.