Volume 33, Issue 2

Objectives Post-traumatic Stress Disorder (PTSD) is a diagnosis of extreme anxiety caused by a traumatic event. Less than 10% of individuals who have experienced severe trauma will develop this disorder. Treatment options include various psychotherapies, but not all patients respond to them. Different pharmacological approaches have been explored as potential adjuvants, including using cannabinoids to target the endocannabinoid system to reduce the symptoms and enhance extinction training over the associated fear memories. This review was aimed to determine the effects of using cannabinoids for treatment of PTSD. Content For this review, four cohort studies, four randomized clinical trials, one case report, and one case series were obtained from PubMed within the last 10 years. Cannabis extracts, tetrahydrocannabinol (THC) and cannabidiol (CBD), and synthetic cannabinoids were used in the studies to target the cannabinoid receptors 1 and 2. Cannabinoids were shown to improve overall PTSD symptoms, including sleep quality and quantity, hyperarousal, and treatment-resistant nightmares. When participants were undergoing extinction training, cannabinoids given within the same time interval enhanced consolidation and retention. Summary and Outlook Cannabinoids have been shown to be an effective treatment option for patients with PTSD. Besides aiding to relieve the symptoms and enhance extinction training, they also are relatively well tolerated. Common adverse effects included light-headedness, forgetfulness, dizziness, and headaches.

The review describes botanical aspects, bioactive phytocompounds and pharmacological properties of different parts of Pithecellobium dulce , with special emphasis on the nutritional status of its fruits. The different parts of plant extract have been reported to possess anti-oxidant, anti-inflammatory, anti-microbial, anti-diabetic, cardio protective, anti-diarrhoeal, anti-ulcerogenic, larvicidal and ovicidal activities. Different parts of plant extracts were reported to contain several bioactive phytocompounds such as flavonoids, saponins, tannins, alkaloids etc. Natural products discovered so far served as a viable source for new drugs. Over the past few years, continued and perpetual attention of people has been paid to medicinal plants in connection with its remarkable importance in drug discovery. Plant products always remains a drug of choice for the identification of novel leads despite facing a tough competition from existing synthetic alternatives derived from combinatorial chemistry, owing to their efficacy, side effects, and safety. P. dulce is a highly acclaimed genus in traditional system of medicine because of its versatile nutraceutical and pharmacological properties. In this review we discuss in detail about nutritional and various therapeutic properties of P. dulce .

Objectives Protocatechuic acid (PCA) possesses numerous pharmacological activities, including antioxidative and anti-inflammatory activities. This study seeks to investigate its underlying mechanism of action in the liver and brain toxicity induced by CCl 4 in male albino rats. Methods Rats were given PCA at 10 and 20 mg/kg daily and orally as a pretreatment for seven days. A single injection of CCl 4 was given 2 h later to induce brain and liver toxicity. Results CCl 4 moderately elevated the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). PCA lowered AST level significantly when compared to control. Total protein and albumin levels presented insignificant changes (p>0.05) in all groups while lipid profile showed increased total cholesterol level and reduced high-density lipoprotein (HDL) by CCl 4 . PCA (10 mg/kg) significantly reduced the cholesterol level while the 20 mg/kg dose moderately prevented HDL reduction. There was an increased MDA production with a corresponding low GSH level in the group treated with CCl 4 . Activities of superoxide dismutase, catalase, and glutathione-S-transferase in both organs also declined. PCA, especially at 10 mg/kg attenuated lipid peroxidation by increasing GSH level in the organs. Biochemical assays revealed the improvement of antioxidant enzyme activities by PCA in these organs. Furthermore, PCA lowered the level of proinflammatory cytokine COX 2 in the brain and liver while NF-kB expression was inhibited in the brain. Histopathology reports validated the effects of PCA. Conclusions PCA exhibited protection against toxicity in these tissues through antioxidant and anti-inflammatory activities and the potential mechanism might be through modulation of the NF-κB/COX-2 pathway.

Objectives Emerging shreds of evidence indicates that the risk of diabetic foot ulcer and associated morbidity can be reduced through the intensive glycemic control. There are very few studies which assessed the effects of glycemic control on diabetic foot problems among Indian patients. We aimed to assess the effect of glycemic control on the outcomes of diabetic foot problems among adult type 2 diabetes (T2DM) patients with foot ulcers. Methods A cross sectional study was conducted among the T2DM patients from a tertiary care teaching hospital in South India. The demographic characters, risk factors, treatment characters, glycemic status were collected among the patients and analyzed against the outcomes of diabetic foot ulcers by reviewing their medical records. Descriptive statistics were used to present the data. The Chi-square test and ANOVA were used for was used for the categorical variables and continuous parameters to identify the factors affecting the outcomes, respectively. All analysis was performed in SPSS v21. Results Out of the 100 participants included in the study, 70% were male. The majority (78%) were from an age group of 40 to 70 years, and the mean age was found to be 59.91 ± 10.6 years. The mean duration of diabetes was 9.66 years. Only ankle-brachial Index score (p=0.001) was significantly associated with the type of ulcers, whereas other factors not (p>0.05). A high level of average HbA 1c , BMI, ABI index and poor glycemic status was associated with a significant debridement strategy and longer duration of hospitalization; however, it was not substantial. Conclusion Our study inferred that poor glycemic status is associated with a significant debridement strategy and longer duration of hospitalization. However, these findings need to be strengthened with adequately powered prospective studies.

Objectives Piperine (1-piperoyl piperidine), a major alkaloid constituent of Piper nigrum L. and Piper longum L. has pleiotropic biological effects, but the mechanism(s) involved remain to be elucidated. The current study was conducted to examine the efficacy of antioxidant ability of piperine on t-BHP induced markers of oxidative stress in human erythrocytes. Methods Healthy human erythrocytes and erythrocytes membrane was stressed with free radical inducer chemical; t- BHP (10 −5  M), and the effects of piperine was measured against free radical mediated modification in lipid and protein content, –SH and GSH value with antioxidant potential. Results The results demonstrate that treatment of erythrocytes with piperine (10 −5 to 10 −7  M) significantly (p<0.05) ameliorated the adverse consequences of oxidative stress as evidenced by prevention of oxidation of erythrocyte reduced glutathione, membrane thiols, proteins, and peroxidation of lipids; the effects were in correlation with ferric reducing and radical scavenging abilities of piperine. Conclusions The study concludes that piperine possesses potent anti-oxidant potential which may explain many of its observed biological effects.

Objectives One of the most important problems of hemodialysis (HD) patients is anorexia due to the lack of proper treatment for it and on the other hand kidney disease is increasing. We designed a randomized controlled clinical trial to investigate the effects of Artemisia supplementation on anorexia in HD patients. Materials and methods This randomized, double-blind, placebo-controlled trial was carried out on 58 subjects with HD, aged 55–65 years old. Participants were randomly divided into two groups. One group received 250 mg/day of Artemisia supplement capsule for six weeks (n=26), and the other group was given placebo for the same time duration and dosage (n=32). The serum concentrations of urea, creatinine, albumin and hemoglobin were measured enzymatically using commercial kits. Anorexia score was measured using a Simplified Nutritional Appetite Questionnaire (SNAQ). Independent t-test analysis were applied to evaluate the data Results The results showed that the Artemisia supplementation significantly improved the anorexia in HD patients, for six weeks (p<0.05). However, it did not significantly effect on the albumin, hemoglobin, urea, creatinine, arm circumference, and body mass index (p>0.05). Conclusion According to the outcomes of this study, Artemisia supplementation can be effective as an adjunct therapy for improve anorexia in HD patients.

Objectives The use of standard antimalarial drugs, such as dihydroartemisinin-piperaquine (DHP) for the treatment of malaria during pregnancy is limited due to the risk of teratogenicity. The alternative is therefore required although few exist. Here we show a phytopharmaceutical drug derived from Andrographis paniculata (AS201-01), which is effective as herbal antimalarial both in vitro and in vivo and may be a suitable alternative when used in complementary treatment with DHP. Methods Plasmodium berghei infected pregnant BALB/c mice were divided into four groups: G1 (negative control), G2 (AS201-01), G3 (DHP), and G4 (combination of DHP and AS201-01). Pheripheral blood was collected during therapy for counting parasitemia. Placental samples were analyzed for the expression of IFN-γ, TNF- α, IL-10, placental parasite counts and foetal morphology. Results Groups G4 and G3 both showed a 100% inhibition of peripheral parasitemia. However, the treatment in G4 was found to be less effective than that in G2 and G3 in preventing placental parasitemia. The G4 treatment was able to reduce the expression of IFN-γ and IL-10, whereas TNF-α was not significantly different from the control group. Foetal morphologic abnormalities were observed in all groups except G2; G4 showed lower percentage of abnormalities compared to G3 and G1. Conclusions A combination of A. paniculata tablet (AS201-01) with DHP has the potential to reduce the toxicity of DHP in malaria treatment.

Objectives The study aimed to compare the levels of anti-inflammatory interleukin-2 (IL-2) and proinflammatory interleukin-18 (IL-18) among newly diagnosed type 2 diabetes mellitus (T2DM) and nondiabetic volunteers, to predict their roles as markers in the diagnosis of newly diagnosed T2DM. Methods In the study, 60 subjects were enrolled (30 T2DM cases and 30 non-diabetic controls). Biochemical parameters such as fasting plasma glucose (FBS), glycated haemoglobin (HbA 1c ), high sensitivity C-reactive protein (hs-CRP) and lipid profile were estimated in auto-analyser. Serum IL-2 and IL-18 levels were assessed by enzyme-linked immune sorbent assay (ELISA). Results Significant differences were observed in the levels of interleukins among study groups. The median (95% confidence interval) of IL-2 in cases and controls were 8.55 (6.07–47.23) and 45.87 (12.81–145.4) (p=0.02). The median (95% CI) of IL-18 on the other hand in cases and controls were 691.6 (580.3–872.6) and 511.1 (452.6–557.5) (p=0.0014). Conclusions Our study is the first to correlate IL-2 and IL-18 in newly diagnosed T2DM patients. Findings from this study highlight the anti-inflammatory role of IL-2 and proinflammatory role of IL-18 in T2DM. ROC analysis helped predict their role as markers in T2DM diagnosis.

Objectives Metals including lead (Pb), aluminum (Al), and zinc (Zn) are widely used in factories such as welding, handicrafts, and paint. Occupational exposure to such metals causes a wide range of biological effects, depending upon the metal levels and duration of exposure. Accumulation of these metals may lead to several adverse health effects such as neurodegenerative diseases and cancer. The study aimed to evaluate Pb, Al, and Zn levels in occupationally exposed workers of North-Western India and create awareness about its toxicity and adverse outcomes. Methods The study included 120 factory workers (exposed) and 100 healthy controls (nonexposed); age ranged 18–78 years. Blood Pb and serum Al was estimated by graphite furnace atomic absorption spectrophotometry and serum Zn was estimated by flame atomic absorption spectrophotometry (ICE 3000, Thermo Fisher Scientific). Results Results indicated significantly higher levels of Pb, Al, and Zn in the exposed than the nonexposed. No significant difference was observed in metal levels, based on age and duration of exposure. Painters showed higher blood Pb, whereas welders were found to have higher serum Al and Zn levels. Conclusions To conclude, workers showed higher levels of metals and it may cause deleterious effects on the health of workers occupationally exposed to these metals. Appropriate maintenance regarding worker’s safety and hygiene is required to protect them from the harmful effects of these toxic metals.

Objectives Reproduction is one of the physiological functions that are often negatively affected by chronic stress. We aimed to examine effects of two distinct 7-day chronic immobilization stress (IMO) models on gonadotropins levels and depression-like behaviors in female rats. Methods Adult Wistar albino female rats were divided into three groups as follows (n=7 for each group): control, IMO-1 (45 min daily for 7-day) and IMO-2 (45 min twice a day for 7-day). Neuropsychiatric behaviors were determined by using forced swimming test (FST) and open field test (OFT). Gonadotropins were analyzed using ELISA tests. Results In FST, swimming was lower, and immobility was higher in the IMO-1 group and IMO--2 group. Climbing score of the IMO-2 group was higher compared to the control group. In OFT, there was no significant alteration in the mean velocity, total distance, duration of time spent in the central area and duration of latency in the central area between the stress groups and the control group. Final body weight and percentage of body weight change were lower in both stress groups. The follicle-stimulating hormone level was lower only in the IMO-2 group, and the luteinizing hormone concentrations were significantly lower in the IMO-1 group and IMO-2 group. Conclusions Our results indicated that depression-like behaviors increased, and gonadotropins decreased in the female rats exposed to 7-day chronic IMO.

Objectives Hypertension is a very common cardiovascular disease. Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) are widely used to treat hypertension. Many patients with hypertension are vulnerable to the antihypertensive adverse effects, which potentially reduces the adherence rate. Therefore, we conducted this study in order to evaluate the safety profile of both classes (ACEi and ARBs) on respiratory functions. Methods Two main groups of subjects were studied: first group is healthy control subjects and the second group is hypertensive patients, which was subdivided into subgroups in order to investigate the effect of all tested medications (captopril, enalapril, lisinopril, losartan, and valsartan). Respiratory efficiency was evaluated by measuring pulmonary function tests: FEV1, FVC, and FEV1%. Measurements were done using micromedical spirometer. Results We found that ARBs do not impair normal respiratory functions as measured by FEV1, FEV1%, and FVC in hypertensive patients. While ACEi treatments significantly reduced FEV1, FEV1%, and FVC compared to the other groups. Conclusions ARBs are not associated with any harmful effects on respiratory functions in hypertensive patients, unlike ACEi. As such, they could represent a first-choice treatment for hypertensive patients who are at high risk to the respiratory adverse effects.

Objectives There has been increasing recognition of the significant relationship between the autonomic nervous system and cardiovascular sequel in diabetes mellitus (DM) patients. Diabetic cardiac autonomic neuropathy (DCAN) still poses a treatment challenge in the clinical settings despite several research interventions. This study was designed to investigate the effect of carvedilol on experimentally induced DCAN in type 2 DM rat model. Methods DCAN was induced in 42 Wistar rats using high fat diet (HFD) for eight weeks, thereafter streptozotocin (STZ) at 25 mg/kg daily for five days. DCAN features were then assessed using non-invasive time and frequency varying holter electrocardiogram (ECG), invasive biomarkers, cardiac histology and cardiac nerve density. Results Carvedilol significantly ameliorated the effects of DCAN on noradrenaline (p=0.010) and advanced glycated end products (AGEs) (p<0.0001). Similarly, carvedilol reversed the reduction in levels of antioxidants, sorbitol dehydrogenase (SD) activity (p=0.009) nerve growth factors (p<0.0001) and choline acetyl-transferase (p=0.031) following DCAN induction. Furthermore, heart rate variability (HRV) indices which were also reduced with DCAN induction were also ameliorated by carvedilol. However, carvedilol had no significant effect on cardiac neuronal dystrophy and reduced cardiac nerve densities. Conclusions Carvedilol improves physiological HRV indices and biomarkers but not structural lesions. Early detection of DCAN and intervention with carvedilol may prevent progression of autonomic neurologic sequel.