Christmas article: Well-being in hot weather ­ a randomised crossover trial.

Introduction While some studies have investigated the cooling properties of warm beverages, no studies have examined thermal well-being in warm environments in relation to beverage temperature. Methods Thirty researchers were randomised in a 1:1 ratio in a double-blinded cross-over study. Participants were randomised to drink 10cl of 10°C and 50°C decaffeinated tea, 15 minutes apart while staying outside in the Turkish summer heat at noon. Well-being was assessed using the American Society of Heating, Refrigeration and Air-conditioning Engineers (ASHRAE) thermal sensation scale, Bedford thermal comfort scale, Brief Mood Introspection Scale (BMIS), and the last two domains of EuroQol 5-domain, 5-point scale: EQ-5D-5L. Results Neither clinically nor statistically significant differences were found in well-being between warm and cold tea. Moods soured significantly as the trial course passed (using BMIS, µ 1.9; P=0.03), but comfort in the heat bettered (using Bedford, µ -0.37; P less-than 0.001). These changes were not considered to be clinically significant. Conclusion We were unable to show any correlation between beverage temperature and comfort in a hot environment. The mood of participants did, however, deteriorate as time passed-a lesson to any future researchers conducting drawn-out experiments just before lunch. Funding none. Trial registration NCT05900960.

Effect of topical application of melatonin cream 12.5% on cognitive parameters: A randomized, placebo-controlled, double-blind crossover study in healthy volunteers.

BACKGROUND: Skin cancer is an increasing problem in modern dermatology. Earlier studies have shown protective effects against ultraviolet radiation (UVR)-induced skin damage by topical treatment with melatonin. However, the potential sedative effects of full body topical application of melatonin have never been investigated. Objectives The aim of this study was to assess the degree of cognitive dysfunction when using melatonin cream as full body topical application. METHODS: In a randomized, placebo-controlled, double-blind crossover study in healthy volunteers, the degree of cognitive dysfunction when using cream containing 12.5% melatonin as full body application was assessed. A group of ten volunteers had melatonin cream 12.5% applied on 80% of their body surface area, and degree of cognitive dysfunction was assessed using a test battery consisting of Karolinska sleepiness scale (KSS), Finger tapping test (FTT) and Continuous Reaction time (CRT). RESULTS: No significant effects on cognitive parameters were found. However, great inter-individual variations on cognitive parameters were observed. CONCLUSION: This study was the first to assess degree of cognitive dysfunction resulting from application of melatonin cream on a full body surface area. The results support that melatonin is a safe drug for dermal application even in a high dosage.

Pharmacokinetics of high-dose intravenous melatonin in humans.

This crossover study investigated the pharmacokinetics and adverse effects of high-dose intravenous melatonin. Volunteers participated in 3 identical study sessions, receiving an intravenous bolus of 10 mg melatonin, 100 mg melatonin, and placebo. Blood samples were collected at baseline and 0, 60, 120, 180, 240, 300, 360, and 420 minutes after the bolus. Quantitative determination of plasma melatonin concentrations was performed using a radioimmunoassay technique. Pharmacokinetic parameters were estimated by a compartmental pharmacokinetic analysis. Adverse effects included assessments of sedation and registration of other symptoms. Sedation, evaluated as simple reaction times, was measured at baseline and 120, 180, 300, and 420 minutes after the bolus. Twelve male volunteers completed the study. Median (IQR) Cmax after the bolus injections of 10 mg and 100 mg of melatonin were 221,500.0 (185,637.5-326,175.0) pg/mL and 1,251,500.0 (864,375.0-1,770,500.0) pg/mL, respectively; mean (SD) t1/2 was 42.3 (5.6) minutes and 46.2 (6.2) minutes; mean (SD) Vd was 1.6 (0.9) L/kg and 2.0 (0.8) L/kg; mean (SD) CL was 0.0253 (0.0096) L/min · kg and 0.0300 (0.0120) L/min · kg; and median (IQR) AUC0- ∞ , 8,997,633.0 (6,071,696.2-11,602,811.9) pg · min/mL and 54,685,979.4 (36,028,638.6-105,779,612.0) pg · min/mL. High-dose intravenous melatonin did not induce sedation, evaluated as simple reaction times. No adverse effects were reported in the study.

Effect of melatonin on human nighttime endotoxaemia: randomized, double-blinded, cross-over study.

BACKGROUND: Endotoxaemia is widely used as an experimental model to study sepsis under controlled conditions. Nighttime endotoxaemia induces a more pronounced inflammatory stress response compared to daytime. Previously, we have shown that melatonin has antioxidative and anti-inflammatory effects in inflammatory response to daytime endotoxaemia. Herein, we examined the effect of melatonin in response to human nighttime endotoxaemia. PATIENTS AND METHODS: Twelve healthy male volunteers were enrolled in a randomized, placebo-controlled, double-blinded cross-over trial. Subjects were induced by lipopolysaccharide (LPS) endotoxin 0.3 ng/kg body weight intravenously at 24:00. One hour prior to induction of endotoxaemia, an 8-h infusion of melatonin 100 mg or placebo was initiated. Blood samples were drawn before and 2, 4, 6 and 8 h after induction of endotoxaemia and plasma was tested for pro-inflammatory markers (tumor necrosis factor alpha, TNF-α, interleukin-1ß, IL-1ß, interleukin-1, IL-6, and YKL-40), anti-inflammatory markers (interleukin-1 receptor antagonist, IL-1Ra, interleukin-10, IL-10, soluble tumor necrosis factor receptors I and II, sTNF-RI and sTNF-RII), marker for oxidative damage (malondialdehyde (MDA)) and antioxidative enzyme (ascorbic acid (AA) and dehydroascorbic acid (DHA)). RESULTS: Compared to placebo, melatonin did not reduce plasma levels of any of pro- and anti-inflammatory markers and it also failed to influence levels of AA, DHA and MDA. CONCLUSION: Melatonin has no beneficial effect on inflammation and oxidative damage induced by nighttime endotoxaemia in contrast to daytime endotoxaemia.

Melatonin does not affect oxidative/inflammatory biomarkers in a closed-chest porcine model of acute myocardial infarction.

AIM: To test whether melatonin reduces oxidative and inflammatory biomarkers in a closed-chest porcine model of acute myocardial infarction. MATERIALS AND METHODS: Twenty pigs were randomized to receive a total dosage of 200 mg (0.4 mg/ml) of melatonin, or placebo immediately prior to reperfusion of a coronary artery balloon occlusion in a randomized, observer-blinded, placebo-controlled trial. We assessed high-sensitivity troponin T (hs-TnT), malondialdehyde and interleukin-1b, -6 and -10 at baseline, 30 min and 1, 2, 3 and 4 h after the start of reperfusion. RESULTS: Seventeen pigs completed the trial. There was an increase in hs-TnT, but no significant difference between the melatonin-treated and placebo-treated groups. There were no significant differences in development of any of the circulating plasma markers between the two groups. CONCLUSION: Melatonin treatment did not result in reduction of inflammatory or oxidative stress markers after experimental myocardial infarction compared to placebo.

Reduced oxidative stress in STEMI patients treated by primary percutaneous coronary intervention and with antioxidant therapy: a systematic review.

PURPOSE: Coronary reperfusion by primary percutaneous coronary intervention (PCI) has been established as an essential therapy of ST-elevation myocardial infarction (STEMI). Although the coronary intervention is undoubtedly beneficial, reperfusion itself can induce processes resulting in additional myocardial damage-a phenomenon known as ischemia-reperfusion injury (IRI). Oxidative stress is one of the major factors contributing to IRI. This systematic review focuses on the effect of antioxidant therapy on reperfusion triggered oxidative stress and myocardial IRI in patients with STEMI. METHODS: We performed a systematic search in EMBASE and Pubmed and included eight randomised clinical trials evaluating edaravone, allopurinol, vitamin c, nicorandil, N-acetylcysteine, glucose-insulin-potassium, atorvastatin and deferoxamine. RESULTS: Administration of edaravone, allopurinol, atorvastatin and nicorandil as a supplement to primary PCI significantly reduced oxidative stress and myocardial damage as well as improved cardiac function and clinical outcomes. Treatment with deferoxamine and N-acetylcysteine reduced the oxidative stress but an effect on the clinical outcome parameters could not be shown. CONCLUSIONS: Preliminary studies of edaravone, allopurinol, atorvastatin and nicorandil seems promising though larger clinical trials with a wider range of clinical outcome parameters and trials of higher methodological quality should confirm the clinical benefits before a general recommendation can be given. Moreover, the included studies revealed a complex link between oxidative stress and cardiac function and/or cardiac adverse events and in order to further elucidate the detrimental role of oxidative stress in IRI in relation to primary PCI the assessment of oxidative stress and the clinical outcome parameters should be standardized.

Lower reoperation rates with the use of fibrin sealant versus tacks for mesh fixation.

BACKGROUND: Groin hernia repair may be associated with long-term complications such as chronic pain, believed to result from damage to regional nerves by tissue penetrating mesh fixation. Studies have shown that mesh fixation with fibrin sealant reduces the risk of these long-term complications, but data on recurrence and reoperation rates after the use of fibrin sealant compared with tacks are not available. This study aimed to determine whether fibrin sealant is a safe and feasible alternative to tacks with regard to reoperation rates after laparoscopic groin hernia repair. METHODS: The current study compared reoperation rates after laparoscopic groin hernia repair between fibrin sealant and tacks used for mesh fixation. The study used data collected prospectively from The National Danish Hernia Database and analyzed 8,314 laparoscopic groin hernia repairs for reoperation rates. Mesh fixation was performed with fibrin sealant (n = 784) or tacks (n = 7,530). RESULTS: The findings showed a significantly lower reoperation rate for the fibrin sealant than for the tacks (0.89 vs 2.94 %, p = 0.031). The median follow-up period was 17 months (range, 0-44 months) for the fibrin sealant group and 21 months (range, 0-44 months) for the tacks group. CONCLUSIONS: Fibrin sealant was superior to tacks for mesh fixation in laparoscopic groin hernia repair with regard to reoperation rates. The study could not differentiate between different hernia defect sizes, and future studies should therefore explore whether the superior effect of fibrin sealant applies for all hernia types and sizes.

Acute abdomen and perforated bowel with a rare pathology: nonfamilial visceral myopathy.

Visceral myopathy is a rare chronic disease affecting the peristalsis of the bowel causing intermittent pseudoobstruction. We report an atypical case of an eighty-nine-year-old woman with no prior history of abdominal illness who was admitted to our hospital with 2 days of increasing nausea, abdominal distension, and abdominal pain. On arrival at the hospital, she was critically ill. Abdominal X-ray showed distended loops of the colon and liquid levels resembling colonic obstruction. A subsequent abdominal CT scan confirmed the colonic obstruction. A suspicion of sigmoid volvulus was raised, that is why a barium enema was performed but no lower colonic obstruction could be confirmed. Acute laparotomy showed perforated cecum without intestinal obstruction. Postoperatively, the patient became septic which was fatal for the patient. Pathology gave the diagnosis visceral myopathy. It is very difficult to make the diagnosis clinically and radiologically since visceral myopathy mimics other more common gastrointestinal diseases. It is important to consider visceral myopathy as a possible diagnosis in cases with recurrent episodes of abdominal pain, vomiting, and abdominal distension, but without actual intestinal obstruction.