Band 34, Heft 3

Cadmium(II) is an omnipresent environmental toxicant emitted from various industrial sources and by anthropogenic sources such as smoking. Cadmium(II) enters our body through various sources including contaminated food and drinks and from active or passive smoking. It spares no organs in our body and the calamities it invites include primarily nephrotoxicity, osteotoxicity, teratogenicity, endocrine disruption, hepatotoxicity and carcinogenicity above all. It brings about a bolt from the blue in the cellular biochemistry by generating reactive oxygen species (ROS), disrupting the factors involved in the repair of DNA lesions and many other toxic nuisances otherwise by modulating the cell signalling machinery and acting as a potent carcinogen above all. In this review, we have tried to decipher some of the mechanisms played by cadmium(II) in exhibiting its toxic effects on various system of our body.

Nasopharyngeal carcinoma (NPC) is a malignant tumor that grows from the epithelial cells of nasopharynx. NPC has the ability to modify its metabolism and leads the patient to suffer from malnutrition and cachexia, therefore aggravates the occurrence of impaired inflammatory response. Currently, available treatments for NPC are chemotherapy, radiotherapy, or chemoradiotherapy. Despite of its efficacy, these regimens have been known to elicit various inflammation-related side effects including infection, diarrhea, and mucositis. It has long been established that increased activity of inflammatory response is associated to low survival rate in both early and advanced stage of cancer. Furthermore, uncontrolled and dysregulated inflammatory response are significantly correlated with malignant progression of cancer. Considering how pivotal inflammation to malignancy progression, there is a need for effective strategies to modulate inflammatory response. Various strategies have been proposed to improve immune response in NPC patients including dietary supplementation of synbiotics. Synbiotics refers to the manipulation of both probiotics and prebiotics to provide a synergistic benefit to the host by promoting the growth of beneficial bacteria while inhibiting the growth of pathogenic bacteria. There is a growing number of evidences related to the potential of synbiotics in modulating the pro-inflammatory response and improve immune systems in a variety of conditions, including cancer. In this study, we will discuss the immunomodulatory effects of synbiotics in the nasopharyngeal carcinoma occurrences.

Ageing is the process generated by senescent cells, free radicals, inflammation and other relevant factors. Ageing contributes to age-related diseases that affect the quality of life. People are interested in anti-ageing intervention and many scientists attempt to search for anti-ageing medicines. This review focused on describing in vivo anti-ageing activity of US-FDA-approved drugs and found that alogliptin, canagliflozin and metformin might produce anti-ageing activity via AMPK activation. Rapamycin and canagliflozin are capable to inhibit mTOR to promote lifespan. Atracurium, carnitine and statins act as DAF-16 activators, which potentially contribute to anti-ageing activity. Hydralazine, lisinopril, rosiglitazone and zidovudine may help stabilize genomic integrity to prolong life expectancy. Other indirect mechanisms, including insulin-lowering effect by acarbose and calcium channel blocking activity by verapamil may also promote longevity. Interestingly, some drugs (i.e., canagliflozin, metformin, rapamycin and acarbose) are likely to demonstrate a lifespan-promoting effect predominantly in male animals. These pre-clinical data might provide mechanistic and phenotypic perspectives to better understand the targets of anti-ageing interventions.

Uterine fibroids (UFs), leiomyomas or myomas, are a type of malignancy that affects the smooth muscle of the uterus, and it is most commonly detected in women of reproductive age. Uterine fibroids are benign monoclonal growths that emerge from uterine smooth muscle cells (myometrium) as well as fibroblasts. Uterine fibroid symptoms include abnormal menstrual bleeding leading to anaemia, tiredness, chronic vaginal discharge, and pain during periods. Other symptoms include protrusion of the abdomen, pain during intercourse, dysfunctions of bladder/bowel leading to urinary incontinence/retention, pain, and constipation. It is also associated with reproductive issues like impaired fertility, conceiving complications, and adverse obstetric outcomes. It is the leading cause of gynaecological hospitalisation in the American subcontinent and a common reason for the hysterectomy. Twenty-five percent of the reproductive women experience the symptoms of uterine fibroids, and among them, around 25% require hospitalization due to the severity of the disease. The frequency of the disease remains underestimated as many women stay asymptomatic and symptoms appear gradually; therefore, the condition remains undiagnosed. The exact frequency of uterine fibroids varies depending on the diagnosis, and the population investigated; nonetheless, the incidence of uterine fibroids in reproductive women ranges from 5.4 percent to 77 percent. The uterine fibroid treatment included painkillers, supplementation with iron, vitamin D3, birth control, hormone therapy, gonadotropin-releasing hormone (GnRH) agonists, drugs modulating the estrogen receptors, and surgical removal of the fibroids. However, more research needed at the level of gene to get a keen insight and treat the disease efficiently.

Moderate-to-vigorous physical activity (MVPA) has been shown to have a favorable effect on many diseases as a complementary therapy and is a critical component of healthy living. During the pandemic era, physical activity has been promoted for resistance against coronavirus disease 2019 (COVID-19). However, there is scarce evidence on whether MVPA could reduce the infectivity and susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The objective of this meta-analysis was to determine the effect of MVPA on morbidity, mortality, and duration of hospitalization in COVID-19 patients. We performed a comprehensive search of five online databases for eligible studies up to September 9, 2021. Meta-analyses were conducted to determine the association between MVPA and COVID-19-related morbidity, hospitalization, and mortality. The odds ratio (OR) was applied as the summary statistic for the primary outcomes. Secondary analyses were conducted to evaluate the difference in the metabolic equivalent of tasks (METs) between the outcome and non-outcome groups with the mean difference as the pooled effect. This meta-analysis included eight observational studies. We found that MVPA significantly reduced the odds of contracting SARS-CoV-2 infection (OR=0.88; 95% confidence interval [CI] = 0.85–0.92), hospitalization (OR=0.56; 95% CI=0.35–0.92), and mortality (OR=0.42; 95% CI=0.21–0.81) due to COVID-19 compared to no physical activity. METs≥500 min/week were linked to decreased morbidity and mortality of COVID-19 (OR=0.94 [95% CI=0.90–0.98]; OR=0.56 [95% CI=0.38–0.83]). COVID-19 patients with MVPA demonstrated a lower risk of COVID-19-related morbidity, hospitalization, and mortality compared to those who were less active, highlighting the importance of an active lifestyle despite the pandemic situation where such activities are limited.

Objectives Ventilator-associated pneumonia (VAP) is the most common nosocomial infection in patients requiring mechanical ventilation in intensive care units (ICUs). VAP is associated with delayed extubation, prolonged hospital stays, increased healthcare costs and mortality rates. The aims of this study to evaluate the level of knowledge for the prevention of VAP among healthcare workers (HCWs) in ICUs and to assess their knowledge in relation to their socio-demographic characteristics. Methods A descriptive, cross-sectional design was conducted to assess HCWs’ knowledge of the guidelines for prevention of VAP in the ICUs of public and private hospitals in Hodeida city, Yemen. Around 140 self-administered multiple-choice questionnaires were distributed between April and July 2017. Results A total of 120 (85.6%) HCWs completed questionnaire were obtained (20 physicians, 20 anesthesia technicians and 80 nurses) in this study. The total mean score of the HCWs’ knowledge was low (41 ± 18). A statistically significant difference was found in the HCWs’ knowledge scores according to their specialties and gender. Anesthesia technicians had the highest knowledge score followed by physicians and nurses (52.2 ± 16.2, 45.6 ± 21.2 and 37.1 ± 16.9, respectively, p=0.002). Males had higher scores than females (Median [IQR] 4 [3–5] vs. 3 [2–4], p<0.001). Participants who received information about the prevention of VAP had better knowledge than those who did not (46.2 ± 17.7 vs. 36.8 ± 17.3, p=0.006). Conclusions HCWs had a low knowledge level of the guidelines for the prevention of VAP, which may affect their practice. HCWs’ knowledge was affected by their previous received information that increases the necessity to provide them with regular in-service education and training programs.

Objectives Autonomic imbalance is attributed as key mechanism altering metabolic regulation in diabetes mellitus. In view of controversial reports on autonomic function in FDRD and prediabetes, we aimed to assess and compare the autonomic function across the complete glycaemic spectrum in Indian population. Methods Short term heart rate variability and cardiac autonomic reactivity tests – blood pressure and heart rate response to orthostatic tolerance and deep breathing exercise, and diastolic response to isometric handgrip exercise were recorded in normoglycemic apparently healthy individual, normoglycemic first degree relatives of diabetes, prediabetes and diabetes individuals. Results Resting heart rate is significantly higher in FDRD, prediabetes and diabetes as compared to controls (control < FDRD = prediabetes = diabetes). Total power, LF power (control < FDRD < prediabetes = diabetes) and HF power (control < FDRD < prediabetes < diabetes) decreased along the glycaemic spectrum. Time-domain variables of HRV (SDNN, RMSSD, NN50, pNN50) were reduced as we move along the glycaemic spectrum (control < FDRD < prediabetes = diabetes). Cardiac autonomic function reactivity parameters such as 30:15 ratio and E:I ratio are decreased in prediabetes and diabetes group as compared to control and FDRD group (control = FDRD < prediabetes = diabetes). Diastolic response to isometric hand grip increases along the glycaemic spectrum starting from FDRD (control < FDRD < prediabetes = diabetes). Conclusions Autonomic dysfunction is observed even in first degree relatives of diabetes. Autonomic dysfunction increases as we move along the glycaemic spectrum (control < FDRD < prediabetes < diabetes).

Objectives To assess the predictive value of pre-discharge heart rate variability (HRV) parameters in patients with acute coronary syndrome (ACS) treated by percutaneous coronary intervention (PCI). Methods 145 consecutive male patients with ACS (aged 57.12 ± 10.81 years) were included in this study. Fifteen minutes electrocardiogram recording was done to measure time-domain [standard deviation of N–N intervals (SDNN), root-mean square differences of successive R–R intervals (rMSSD)] and frequency-domain [low-frequency (LF) power, high-frequency (HF) power and total power (TP)] HRV parameters before and after PCI. The primary end point was the occurrence of major clinical events (MCE) defined as death, sudden death or re-acute myocardial infarction at the end of 3 months follow-up. Results At a follow-up of 3 months, MCE occurred in 06 patients (4.14%) (Cardiac death was 3.01%, while that of sudden death was 1.13%). Out of six-MCE, four deaths and two re-AMIs occurred. Pre-discharge HRV values (SDNN, rMSSD, TP, LF and HF) were significantly lower in patients with ACS without MCE. Only total power HRV index (AUC=0.748; p=0.040) showed greater prognostic accuracy. Conclusions In conclusion, study showed an increase in SDNN, rMSSD, LF, HF and TP after successful revascularization with PCI in patients who had MCE. The resultant sensitivity, specificity of HRV is still limited in the present study. Particularly, its sensitivity is higher (33–83%) with a modest specificity (61–72%).

Objectives Acute renal injury (AKI) is a major limiting factor for cisplatin administration. Recent evidence suggests the potential contribution of mesenchymal stem cells (MSCs) to rehabilitation from several disorders via both direct and indirect routes. Thus, the present study aimed, for the first time, to explore and compare the reno-protective potential of human dental pulp-derived stem cells (hDPSCs) vs. hDPSC-conditioned medium (hDPSC-CM) in recovery of impaired kidney tissues in a rat animal model of cisplatin-induced AKI. Methods AKI was induced via cisplatin injection (n=36). One day after, 24 rats were treated with either hDPSCs or hDPSC-CM (n=12). An extra set of rats (n=12) served as sham group. On days 2 or 7 (n=6), rats were humanly sacrificed for further analysis. Renal injury was explored via measuring serum creatinine and BUN. Renal level of oxidative stress was assessed by determining malondialdehyde, and enzymatic activities of superoxide dismutase and catalase. Renal histopathological changes were scored for comparison among different experimental groups. Results A single dose of cisplatin resulted in considerable renal dysfunction and oxidative stress. Treatment with hDPSCs or hDPSC-CM resulted in significantly restored renal function, reduced level of oxidative stress, and improved histopathological manifestations. Furthermore, as compared to hDPSC-CM, administration of hDPSCs led to superior results in AKI-induced animals. Conclusions The current study described the first comparative evidence of reno-protective potential of hDPSCs and their CM against cisplatin-induced nephrotoxicity in an AKI rat model, proposing them as useful adjunctive therapy in AKI. Yet, future explorations are still needed.

Objectives Caffeine is the most widely used psychoactive substance in the world. Animal studies indicate that acute caffeine exposure at high doses may induce seizures and diminish the anticonvulsant activity of antiepileptic drugs (AEDs) at much lower doses. The aim of the current study was to assess the effect of caffeine on the anticonvulsant action of levetiracetam (LEV) and vigabatrin (VGB). Methods The anticonvulsant activity of LEV and VGB was examined in the maximal electroshock seizure threshold test in mice (MEST test). All drugs were administered intraperitoneally by single injections, and caffeine was applied at doses capable of interfering with AEDs. Effects of caffeine exposure on AEDs were also investigated in tests of memory and motor performance. Results Caffeine reduced the protective effect of LEV against electroconvulsions. Total brain concentration of LEV was unaffected by caffeine as well as inversely; LEV had no significant impact on the brain caffeine concentration, suggesting a pharmacodynamic nature of the interaction between LEV and caffeine in the MEST test. VGB at applied doses did not affect the convulsive threshold. Administration of VGB, but not LEV, alone or in combination with caffeine, impaired memory retention. In the chimney test, the combined treatment with AEDs and caffeine did not cause motor coordination impairment. Conclusions It is suggested that caffeine may negatively affect the anticonvulsant action of LEV in patients with epilepsy.

Objectives Cardiac surgeries initiate oxidative stress, increasing organ dysfunction development and mortality. The present study investigated the superoxide dismutase (SOD) activity, as an antioxidant enzyme, in patients undergoing coronary artery bypass (CABG) and heart valve replacement surgeries. Methods A prospective study was performed on patients with proven coronary artery disease (CAD) or valvular heart disease (VHD) candidates for on- or off-pump CABG and valve replacement surgery. Serum SOD activity was measured preoperatively, at 24 h postoperatively, and at the time of discharge. In addition, echocardiography was performed before surgery and at discharge. Results A total of 48, 51, and 47 patients were enrolled in the on-pump, off-pump CABG, and valve replacement groups, respectively. Baseline serum SOD activity showed no significant association with BMI, age, and blood pressure in either CAD or VHD patients. The SOD values decreased at the 24 h postoperative time and then increased at the time of discharge in all groups, except for a slight decrease in the on-pump group. The changes in serum SOD values were not significantly different for the three surgical groups. Conclusions The serum SOD activities fell significantly after CABG and valve replacement surgery. Further investigation is emphasized for the role of SOD in oxidative stress after cardiac surgery.

Objectives The objective of the present study was to evaluate the Drug utilisation pattern in patients of diabetic nephropathy (stage 1–4) in a tertiary care hospital in South-Asia. Methods A cross-sectional observational study was conducted in the nephrology out-patient-department of a tertiary care hospital in South-Asia. WHO core prescribing, dispensing, and patient care indicators were evaluated, and adverse drug reactions (ADRs) encountered by the patients were analysed for causality, severity, preventability, and outcome. Results The most commonly prescribed antidiabetics in diabetic nephropathy patients were insulin (17.42%), followed by metformin (4.66%). Current drugs of choice SGLT-2 inhibitors were prescribed in a lesser frequency than expected. Loop diuretics and calcium channel blockers (CCBs) were the preferred antihypertensives. The use of ACE inhibitors (1.26%) and ARBs (3.45%) for hypertension was restricted to Stage 1 and 2 nephropathy. The patients were on 6.47 drugs on average. 30.70% of drugs were prescribed by generic names, 59.07% of the drugs were prescribed from the national essential drugs list and 34.03% of the prescribed drugs were supplied by the hospital. CTCAE grade 1 (68.60%) and grade 2 (22.09%) ADR severity was the highest. Conclusions Prescribing patterns in patients of diabetic nephropathy were adapted from relevant medical evidence, affordability and availability of the drugs. Generic prescribing, availability of drugs and ADR preventability in the hospital have a broad scope for improvement.

Objectives To compare differences of operative outcomes, post-operative complications and survival outcomes between open and laparoscopic cases in a multicenter study. Methods This was a retrospective cohort study performed at three European centers from September 2011 to January 2019. The surgeon decision to perform open inguinal lymphadenectomy (OIL) or video endoscopic inguinal lymphadenectomy (VEIL) was done in each hospital after patient counselling. Inclusion criteria regarded a minimum follow-up of 9 months since the inguinal lymphadenectomy. Results A total of 55 patients with proven squamous cell penile cancer underwent inguinal lymphadenectomy. 26 of them underwent OIL, while 29 patients underwent VEIL. For the OIL and VEIL groups, the mean operative time was 2.5 vs. 3.4 h (p=0.129), respectively. Hospital stays were lower in the VEIL group with 4 vs. 8 days in OIL patients (p=0.053) while number of days requiring drains to remain in situ was 3 vs. 6 days (p=0.024). The VEIL group reported a lower incidence of major complications compared to the OIL group (2 vs. 17%, p=0.0067) while minor complications were comparable in both groups. In a median follow-up period of 60 months, the overall survival was 65.5 and 84.6% in OIL and VEIL groups, respectively (p=0.105). Conclusions VEIL is comparable to OIL regarding safety, overall survival and post-operative outcomes.

Objectives Preliminary research suggests that electrical vestibular nerve stimulation (VeNS) may improve sleep outcomes by influencing the hypothalamus and brainstem nuclei involved in regulating the circadian rhythm and wakefulness. This randomised, sham-controlled trial aimed to assess the effectiveness of VeNS on insomnia in young adults. Methods Eighty adults aged 18–24 years were randomly allocated to the intervention (n=40) and control groups (n=40). The intervention group was provided with 30 min per day of VeNS with five sessions weekly for four weeks, while the control group received sham stimulation for the same period. Baseline Insomnia Sleep Index (ISI) scores were recorded weekly. At baseline and at day 28, questionnaires to evaluate emotional states of depression, anxiety and stress, and quality of life (QoL) were completed. The primary outcome was change in ISI with comparison between baseline and day 28. Results The VeNS group significantly reduced their mean ISI score after 7 days usage (p<0.001). At day 28 it was found that mean ISI scores had reduced from 19 to 11 in the VeNS group, and from 19 to 18 in the sham group, and the difference between the groups was significant (p<0.001). Moreover, application of VeNS appeared to significantly improve emotional state and QoL outcomes. Conclusions This trial demonstrates that regular VeNS usage over four weeks leads to a clinically meaningful decrease in ISI scores in young adults with insomnia. VeNS may have potential as a drug-free and non-invasive therapy to improve sleep outcomes by positively influencing the hypothalamic and brainstem nuclei.

Objectives The use of Bruton’s tyrosine kinase (BTK) inhibitors has changed the clinical history of patients with chronic lymphocytic leukemia (CLL) in both naïve and relapsed/refractory settings. “Accelerated” chronic lymphocytic leukemia (a-CLL) is a relatively rare form of CLL representing less than 1 % of all CLL cases. a-CLL patients usually have a more aggressive course and a reduced overall survival was reported with conventional chemo-immunotherapy approaches. Methods The role of Bruton Tyrosine Kinase-inhibitor, ibrutinib, in a-CLL is well established with encouraging preliminary results. Results We report a case of a-CLL-treated first-line with second-generation BTKi, acalabrutinib with a prompt clinical response. As known, it is the first literature report on acalabrutinib in a-CLL highlighting the role of second-generation BTKi also in this high-risk setting. Conclusions Target therapies (Bruton Kinase inhibitors and Bcl2 inhibitors) have improved the therapeutic landscape of CLL. The availability of therapeutic targets requires greater diagnostic accuracy to choose the most appropriate therapy for each patient.

COVID-19 is a rapidly spreading disease, causing a global pandemic. It is circulating in multiple countries and causing a series of respiratory infections. Due to the uncertain safety and efficacy of the vaccines and lack of specific medicines, it’s important to investigate new pharmacological procedures and find out new drugs that help us eradicate this pandemic. We suggest the hypothesis that Notopterol (NOT), the main Secondary metabolite of Notopterygium incisum Ting ex H.T (a common Chinese medicinal herb), may have the potential benefits on SARS-CoV2 infection for this reasons: (a) NOT exhibits anti-inflammatory, anticancer, and anti-angiogenic properties, (b) NOT indicates a significant reduction in cytokines and chemokines releasing including TNFa, IL-6, interferon-γ, which may decrease COVID-19 cytokine storm (c) NOT can suppress the expression of genes which leads to inflammation via Janus kinase/signal transducers and activators of transcription (JAK-STAT) signaling pathway. It is exactly acting like tocilizumab, (an approved drug against COVID-19) and (d) Notopterygium incisum has antiviral activity against influenza virus, it can reduce the viral-induced oxidative stress. By these explanations, it is hopeful that NOT may be effective in COVID-19 infections which needs further investigations to examine Notopterol as a beneficial agent against the SARS-CoV2 infection.