The involvement of KATP channels in morphine‐induced antinociception and hepatic oxidative stress in acute and inflammatory pain in rats

This study investigated the role of K_ATP channels in morphine‐induced antinociception and hepatic oxidative stress in acute and inflammatory pain. The K_ATP channel modulators (K_ATP channel opener, diazoxide 100 mg/kg, p.o, and K_ATP channel blocker, glibenclamide, 3 mg/kg i.p.) were administered with morphine (80 mg/kg, i.p.). Antinociception was assessed by the tail‐flick and formalin tests in rats and measured by the area under the curve values and the maximum percent effect for 3 h. The indices of hepatic oxidative stress: glutathione, glutathione peroxidase, and malondialdehyde were then determined in the liver homogenates obtained from the treated animals. In both tests, glibenclamide antagonized morphine‐induced antinociception, whereas diazoxide augmented it in the tail‐flick test only. In the formalin test, glibenclamide alone has a significant hyperalgesic effect, whereas diazoxide decreased the number of flinches. Coadministration of glibenclamide with morphine antagonized the hepatotoxic effect of morphine in both animal models. In the tail‐flick test, glibenclamide administered alone significantly increased malondialdehyde's level. Coadministration of diazoxide with morphine increased glutathione level in the formalin test. Diazoxide administered alone exacerbated the hepatic oxidative stress in both animal models. These findings suggest a role of K_ATP channel modulators on morphine‐induced antinociception and hepatic oxidative stress. The administration of glibenclamide may prevent morphine‐induced hepatotoxicity. The effectiveness of diazoxide in the management of pain is limited due to its deleterious effect on the liver. However, the interaction of the K_ATP channel modulators with morphine depends on the differential sensitivity to the pain stimulus.     

Comparative study between atorvastatin and losartan on high fat diet‐induced type 2 diabetes mellitus in rats

Obesity is often associated with chronic inflammatory state which contributes to the development of insulin resistance (IR) and type 2 diabetes mellitus (T2DM). This study investigated the effects of single and combined administration of atorvastatin (ATOR, lipid‐lowering drug) and losartan (LOS, angiotensin receptor antagonist) on metabolic disorders and inflammatory status that are implicated in the development of T2DM with the use of pioglitazone (PIO) as a standard antidiabetic drug. T2DM was induced in male rats by high‐fat diet (HFD) feeding for 16 weeks. Oral administrations of ATOR (10 mg/kg), LOS (20 mg/kg), PIO (3 mg/kg), their binary combinations, or vehicle were started in the last 4 weeks. Fasting serum glucose, oral glucose tolerance, fasting serum insulin, IR, serum lipid profile, serum TNF‐α and body composition index were determined. Results showed that all drugs and their combinations had positive impact effect on all measured parameters, and better results were achieved from binary drug combinations than administration of each drug alone. Combination of PIO with either ATOR or LOS provided better improvements on T2DM‐associated metabolic abnormalities and inflammatory status with respect to each drug alone. However, the most pronounced effects of drugs and their combinations regarding the above parameters were attributed to LOS + PIO combination. In conclusion, this study indicates that combination of ATOR + PIO and, in particular, LOS + PIO can be used as promising effective therapies in the management of HFD‐induced T2DM. This concept may be attributed to the combined effects of the respective monotherapies to improve lipid profile, insulin sensitivity, and TNF‐α level.     

Risk factors for hospital admission among COVID-19 patients with diabetes: A study from Saudi Arabia

Objectives:To elucidate the risk factors for hospital admission among COVID-19 patients with type 2 diabetes mellitus (T2DM).Methods:This retrospective study was conducted at the Prince Sultan Military Medical City, Riyadh, Saudi Arabia between May 2020 and July 2020. Out of 7,260 COVID-19 patients, 920 were identified as T2DM. After the exclusion process, 806 patients with T2DM were included in this analysis. Patients’ data were extracted from electronic medical records. A logistic regression model was performed to estimate the risk factors of hospital admission.Results:Of the total of 806 COVID-19 patients with T2DM, 48% were admitted in the hospital, 52% were placed under home isolation. Older age between 70-79 years (OR [odd ratio] 2.56; p=0.017), ≥80 years (OR 6.48; p=0.001) were significantly more likely to be hospitalized compared to <40 years. Similarly, patients with higher HbA1c level of ≥9% compared to <7%; (OR 1.58; p=0.047); patients with comorbidities such as, hypertension (OR 1.43; p=0.048), cardiovascular disease (OR 1.56; p=0.033), cerebrovascular disease (OR 2.38; p=0.016), chronic pulmonary disease (OR 1.51; p=0.018), malignancy (OR 2.45; p=0.025), chronic kidney disease (CKD) IIIa, IIIb, IV (OR 2.37; p=0.008), CKD V (OR 5.07; p=0.007) were significantly more likely to be hospitalized. Likewise, insulin-treated (OR 1.46; p=0.03) were more likely to require hospital admission compared to non-insulin treated patients.Conclusion:Among COVID-19 patients with diabetes, higher age, high HbA1c level, and presence of other comorbidities were found to be significant risk factors for the hospital admission.     

The role of CC chemokine receptor 5 (CCR5) in islet allograft rejection

Chemokines are important regulators in the development, differentiation, and anatomic location of leukocytes. CC chemokine receptor 5 (CCR5) is expressed preferentially by CD4(+) T helper 1 (Th1) cells. We sought to determine the role of CCR5 in islet allograft rejection in a streptozotocin-induced diabetic mouse model. BALB/c islet allografts transplanted into CCR5(-/-) (C57BL/6) recipients survived significantly longer (mean survival time, 38 +/- 8 days) compared with those transplanted into wild-type control mice (10 +/- 2 days; P < 0.0001). Twenty percent of islet allografts in CCR5(-/-) animals without other treatment survived >90 days. In CCR5(-/-) mice, intragraft mRNA expression of interleukin-4 and -5 was increased, whereas that of interferon-gamma was decreased, corresponding to a Th2 pattern of T-cell activation in the target tissues compared with a Th1 pattern observed in controls. A similar Th2 response pattern was also observed in the periphery (splenocytes responding to donor cells) by enzyme-linked immunosorbent spot assay. We conclude that CCR5 plays an important role in orchestrating the Th1 immune response leading to islet allograft rejection. Targeting this chemokine receptor, therefore, may provide a clinically useful strategy to prevent islet allograft rejection.     

Intracranial meningeal melanocytoma associated with ipsilateral nevus of Ota. Case report

In this report, the authors review the case of a man with a neurocutaneous syndrome. He presented with an intracerebral melanocytoma associated with a blue nevus of the scalp; its location and its appearance during childhood supported the diagnosis of a nevus of Ota. Meningeal melanocytomas are increasingly being diagnosed, but remain rare. Primary meningeal malignant melanoma is the first differential diagnosis to eliminate. Despite their common embryonic origin. the association of a melanocytoma with a nevus of Ota is rare. A nevus of Ota exhibits the same melanocytic proliferation and affects the trigeminal nerve territory. An ocular effect is not always observed. In contrast to an ocular lesion, a nevus of Ota rarely transforms into a malignant melanoma. It is found only among caucasians. During 4 years of follow-up review after surgery, the patient remained asymptomatic. Other than antiepileptic therapy, he received no complementary treatment and cerebral imaging revealed no evidence of recurrence.     

Mitral stenosis after mitral valve repair for non-rheumatic mitral regurgitation

BACKGROUND: Mitral stenosis after mitral valve repair for non-rheumatic mitral regurgitation is rare. METHODS: From 1990 to 1999, 478 patients had mitral valve repair for myxomatous and 40 patients had mitral valve repair for ischemic mitral regurgitation. The Carpentier annuloplasty ring (Edwards Lifesciences, Irvine, CA) was used in 72 patients, the Duran ring (Medtronic, Minneapolis, MN) in 152, a posterior band in 221 and no ring or band in 73 patients. RESULTS: Four patients developed mitral stenosis late after mitral valve repair: 2 for myxomatous disease and 2 for ischemic mitral regurgitation. All 4 patients had Duran annuloplasty rings (sizes 25 to 31). The diagnosis of mitral stenosis was made by Doppler echocardiography. The mitral valve area in these 4 patients decreased from 2.7 cm2 (range, 2.3 to 3.2 cm2) early postoperatively to 0.85 cm2 (0.4 to 1.2 cm2) after a mean follow-up of 66 months (range, 38 to 110 months). Three patients had mitral valve replacement and the etiology of the mitral stenosis was the same in all patients (ie, pannus overgrowth on the annuloplasty ring with extension onto both leaflets rendering them stiff and immobile). The fourth patient had a mitral valve area of 1.2 cm2, which was mildly symptomatic with normal pulmonary artery pressure, and this patient has not had reoperation. CONCLUSIONS: Mitral stenosis may develop after mitral valve repair for myxomatous disease or ischemic mitral regurgitation when a Duran ring is used for annuloplasty. The stenosis is caused by pannus on the annuloplasty ring with extension onto the leaflets.     

Immune response deviation and enhanced expression of chemokine receptor CCR4 in TBI patients due to unknown serum factors

Background

Severe brain trauma leads to an activation of the immune system. To this date, neither the exact perturbation of the specific immune reaction induced by the traumatic brain injury (TBI), nor the interactions leading to the infiltration of peripheral immune cells into the brain are fully understood.

Patients and methods

Serum was collected from 17 patients with TBI and a long bone fracture, 24 patients with an isolated long bone fracture and from healthy individuals. The effect of the serum on normal human monocytes and T-lymphocytes was tested in vitro by assessing proliferation and expression of surface markers, chemokine receptors and cytokines.

Results

Serum collected from patients with a TBI and a long bone fracture increased the expression of the chemokine receptor CCR4 in monocytes when compared to patients with an isolated long bone fracture. Extending this comparison to T-lymphocytes, the serum from TBI patients induced lower proliferation rates and decreased expression of the pro-inflammatory cytokine TNF-α, while simultaneously increasing the secretion of immune-modulatory cytokines (IL-4, IL-10 and TGF-β) (p < 0.05).

Conclusion

Patients with a TBI release currently unknown soluble factors into the circulating blood that up regulate expression of chemokine receptor CCR4 in peripheral blood monocytes whilst concurrently inducing expression of immunosuppressive cytokines by activated T-lymphocytes.     

Effective awake thoracic epidural anesthetic for major abdominal surgery in two high-risk patients with severe pulmonary disease--a case report

Awake thoracic epidural anaesthesia as the sole anaesthetic technique was successfully employed for two high risk surgical patients with chronic obstructive pulmonary disease undergoing abdominal surgery. The procedure was tolerated well and the anaesthetic technique which has been shown to reduce intra-operative and post-operative cardiac, respiratory and gastrointestinal complications, may have significantly contributed to the prompt, complication free recovery experienced by both patients. We report two cases of awake major abdominal surgery in two high-risk surgical patients with severe pulmonary disease, performed effectively under thoracic epidural anaesthesia as a sole technique. The first case was an elective open sigmoid colectomy in a sixty one year old cancerous patient with chronic obstructive pulmonary disease [COPD] and recent thoracotomy for a wedge resection of a bronchial adenocarcinoma [pT1NoMx]. The second case was an emergency open cholecystectomy in an adult patient with end-stage COPD. Reviewing the literature, no similar cases were reported recently.