Volume 32, Issue 2

Hypothyroidism is a clinical syndrome caused by thyroid hormone deficiency due to reduced production, deranged distribution, or lack of effects of thyroid hormone. The prevalence of hypothyroidism in developed countries is around 4–5%, whereas it is about 11% in India, only 2% in the UK, and 4·6% in the USA. It is more common in women than in men. Hypothyroidism has multiple etiologies and manifestations. The most common clinical manifestations are weight gain, loss of hair, cold intolerance, lethargy, constipation, dry skin, and change in voice. The signs and symptoms of hypothyroidism differ with age, gender, severity of condition, and some other factors. The diagnosis is based on clinical history, physical examination and serum level of FT3, FT4, and thyroid-stimulating hormone, imaging studies, procedures, and histological findings. The treatment of choice for hypothyroidism is levothyroxine, however; in this review article, we have discussed the epidemiology, etiology, clinical sign and symptoms, diagnosis, complications, and management of hypothyroidism in modern medicine and a comparative treatment by the Unani system of medicine (USM). In the USM, the main emphasis of the principle of treatment ( Usool-e-Ilaj ) is to correct the abnormal constitution ( Su-e-Mizaj ) and alter the six prerequisites for existence ( Asbab-e-Sitta Zarooriya ) to restore normal health. It is a packaged treatment, that is, different components of treatment are given as a package form which includes different drugs, dosages form, and regimens. Highlights – The concept of hypothyroidism has evolved over the centuries. It has been reported to be a woman-centric disorder. – There are several new subclasses of hypothyroidism based on the site of the lesion. – Levothyroxine has remained the treatment of choice. There has been little progress in managing the disorder. – The Unani system of medicine has been treating various manifestations of the disease since centuries with the help of crude drugs of herbal, animal, or mineral origin. – This review updates the concept and various dimensions of the disease hypothyroidism. – This review has enlisted new modalities for reducing the risk of hypothyroidism as stated in the literature of Unani medicine.

Objectives Parkinson’s disease (PD) is a neurological condition with selective progressive degeneration of dopaminergic neurons. Routine therapies are symptomatic and palliative. Although, hesperidin (Hsd) is known for its neuroprotective effects, its exact cellular mechanism is still a mystery. Considering the important role of calcium (Ca 2+ ) in cellular mechanisms of neurodegenerative diseases, the present study aimed to investigate the possible effects of Hsd on Ca 2+ channels in cellular model of PD and the possible association between the selective vulnerability of neurons in cellular models of PD and expression of the physiological phenotype that changes Ca 2+ homeostasis. Methods SH-SY5Y cell line was used in this study; cell damage was induced by 150 µM 6-OHDA and the cells’ viability was examined using MTT assay. Intracellular calcium, reactive oxygen species (ROS) and mitochondrial membrane potential were determined by the fluorescence spectrophotometry method. The expressions of calcium channel receptors were determined by gel electrophoresis and immunoblotting. Results Loss of cell viability and mitochondrial membrane potential were confirmed in 6-OHDA treated cells. In addition, intracellular ROS and calcium levels, calcium channel receptors significantly increased in 6-OHDA-treated cells. Incubation of SH-SY5Y cells with hesperidin showed a protective effect, reduced the biochemical markers of cell damage/death, and balanced calcium hemostasis. Conclusions Based on our findings, it seems that hesperidin could suppress the progression of the cellular model of PD via acting on intracellular calcium homeostasis. Further studies are needed to confirm the potential benefits of preventive and therapeutic effects of stabilizing cellular calcium homeostasis in neurodegenerative disease.

Objectives Electrical stimulation of the vestibular system (VeNS) has been shown to improve Insomnia Severity Index (ISI) when delivered during sleep. We hypothesize that repeated electrical vestibular stimulation, when delivered prior to sleep onset, will improve ISI scores. The primary aim of this study was to assess the effect that VeNS had on ISI scores when delivered prior to sleep onset. A secondary aim was to provide initial data indicating “length of time to effect” that will allow more appropriate design of a larger randomized control trial (RCT). Methods The present study was an experimental study (pre and post without control). The participants acted as self-controls. After recording the baseline values, electrical vestibular nerve stimulation was administered as intervention once in a day for 30 min, 1 h prior to sleep onset using ML1000 device (Neurovalens, UK) for 14 days. Results There was significant decrease in the ISI scores followed by the electrical vestibular nerve stimulation. Further, participants reported a significant increase in well-rested sleep post the intervention period. Conclusions This study supports our hypothesis that VeNS has a positive impact on ISI scores when delivered on a regular basis prior to sleep onset.

Objectives Previous studies have suggested antidepressant properties for modafinil; however, the underlying mechanisms mediating the antidepressant effect of modafinil have not been well recognized in clinical and animal studies. Nitric oxide (NO) is involved in the pathophysiology of depression. We attempted to investigate the possible role of NO in the antidepressant-like effect of modafinil in mouse forced swimming test (FST) and tail suspension test (TST). Methods The antidepressant-like effect of modafinil (25, 50 and 75 mg/kg), alone and in combination with l -arginine, l -arg, (100 mg/kg) and N G - l -arginine methyl ester, l -NAME (5 mg/kg), was evaluated using FST and TST. Following behavioral tests, the hippocampi were dissected out to measure nitrite levels. Results Findings suggested that administration of modafinil at doses of 50 and 75 mg/kg significantly reduced immobility time in the FST and TST. Furthermore, administration of l -arg and l -NAME increased and decreased, respectively, the immobility time in the FST and TST. We showed that co-administration of a sub-effective dose of modafinil (25 mg/kg) plus l -NAME potentiated the antidepressant-like effect of the sub-effective dose of modafinil. In addition, co-treatment of an effective dose of modafinil (75 mg/kg) with l -arg attenuated the antidepressant-like effect of the effective dose of modafinil. We showed that the antidepressant-like effect of modafinil is associated with decreased nitrite levels in the hippocampus. Conclusions Our findings for the first time support that the modulation of NO, partially at least, is involved in the antidepressant-like effect of modafinil in mouse FST and TST.

Objectives The global increase in various neurological disorders is a serious problem to be concerned. This study mainly focused on the changes in cognitive impairment, sleep pattern, visuospatial ability in the Parkinson’s disease (PD) and its possible association with the usage of smartphones durations. Methods Parkinson’s patients (40–60 years) visiting neurology clinics were included in this study. Based on their age the grouping was designed as Group I (>60) and Group II (40–60 years). All the patients were evaluated for the various motor symptoms in the presence of a neurologist and graded accordingly. The non-motor symptoms included the analysis cognitive function and sleep patterns. The mobile phone usage time was also collected. The Hoehn and Yahr system was used as assessment tool for gradations of PD signs. Results Duration of mobile phone usage in the Parkinson’s patients ranging from 45–60 year was more when compared to the patients aged more than 60 years. The usage of mobile phone did not show significant variation on severity of motor symptoms and cognitive functions. Increased incidence of sleep deprivation was observed in the PD patients aged 40–60 years. Increased usage of mobile phone has been inversely associated with the increased progression of the Parkinson’s disease. Conclusion The present study pointed out the significant association of mobile phone usage with the early onset of Parkinsonism.

Objectives Azodicarbonamide (ADA) is a dough enhancer currently used as a replacement for potassium bromate in the process of bread-making in countries such as Nigeria. However, comprehensive information on the toxicological profile of ADA is not readily available. The present study investigated the toxicological effects of ADA in rats. Methods Twenty-four adult rats were randomly assigned into four groups of six rats each. Animals in group A served as the control (administered standard diet), whereas animals in groups B, C and D were fed ADA in food at 1, 2 and 4%, respectively. Standard or ADA diet was fed to the animals daily for a period of 28 days. Body weight was measured weekly, whereas food and water consumption was measured daily. On day 28, animals were fasted overnight after which they were euthanised. Blood samples taken were used for assessment of fasting blood glucose, haematological parameters, serum lipids, antioxidant status, lipid peroxidation status, electrolytes and urea, plasma proteins and biochemical parameters of liver and kidney injury. The liver and kidneys were then excised and processed for general histological study. Results The results showed that repeated administration of ADA was associated with dose-related decrease in weight gain, decrease in overall food consumption, decreased superoxide dismutase activity/glutathione level and increased lipid peroxidation. There was also biochemical and morphological evidence of liver and kidney injury. Conclusions These findings suggest that food-added ADA could be injurious to the body cells and organs in rats.

Objectives Wound healing is a complex process with a sequence of restoring and inhibition events such as cell proliferation, differentiation, migration as well as adhesion. Mesenchymal stem cells (MSC) derived conditioned medium (CM) has potent therapeutic functions and promotes cell proliferation, anti-oxidant, immunosuppressive, and anti-apoptotic effects. The main aim of this research is to study the role of human umbilical cord-mesenchymal stem cells (UC-MSCs) derived CM in stimulating the proliferation of human keratinocytes (HaCaT). Methods Firstly, MSC were isolated from human umbilical cords (UC) and the cells were then cultured in proliferative medium. We prepared and collected the CM after 72 h. Morphological changes were observed after the treatment of HaCaT cells with CM. To validate the findings, proliferation rate, clonal efficiency and also gene expression studies were performed. Results Increased proliferation rate was observed and confirmed with the expression of Proliferating Cell Nuclear Antigen ( PCNA ) after treatment with HaCaT cells. Cell-cell strap formation was also observed when HaCaT cells were treated with CM for a period of 5–6 days which was confirmed by the increased expression of Collagen Type 1 Alpha 1 chain ( Col1A1 ). Conclusions Our results from present study depicts that the secretory components in the CM might play a significant role by interacting with keratinocytes to promote proliferation and migration. Thus, the CM stimulates cellular proliferation, epithelialization and migration of skin cells which might be the future promising application in wound healing.

Objectives Neurogenesis occurs in the mammalian brain throughout adulthood and increases in response to metabolic, toxic or traumatic insults. To remove potentially superfluous or unwanted neural stem cells/neuronal progenitors, their rate of proliferation and differentiation is fine-tuned against their rate of apoptosis. Apoptosis requires the transcriptional and posttranslational activation of Bcl-2-homolgy domain 3 (BH3)-only proteins. Previously, we demonstrated that the BH3-only protein p53-upregulated mediator of apoptosis (Puma) controls the physiological rate of apoptosis of neural precursor cells in the adult mouse hippocampus. Puma’s role in controlling a lesion-induced increase in neural stem cells is currently not known. Methods We employed a model of local, N-methyl-D-asparte (NMDA)-induced excitotoxic injury to the CA1 hippocampal subfield and immunofluorescence labelling to produce increased neural stem cell proliferation/ neurogenesis in the dentate gyrus at two survival times following the excitotoxic lesion. Results Deletion of puma failed to rescue any NMDA-induced increase in adult born cells as assessed by BrdU or Doublecortin labelling in the long-term. No difference in the proportion of BrdU/NeuN-positive cells comparing the different genotypes and treatments suggested that the phenotypic fate of the cells was preserved regardless of the genotype and the treatment. Conclusions While neurogenesis is up-regulated in puma-deficient animals following NMDA-induced excitotoxicity to the hippocampal CA1 subfield, puma deficiency could not protect this surplus of newly generated cells from apoptotic cell death.

Objectives This study has characterized the phytoconstituents and evaluated the in vitro antioxidant and hepatoprotective effects of Pleurotus tuber-regium induced by carbon tetrachloride (CCl 4 ). In vitro antioxidant assay of ethanol extract of P. tuber-regium and gas chromatography-mass spectrometry analyses to identify the phytoconstituents were carried out. Methods Sixty rats were divided into six groups of 10 animals in each group and treated as follows for 13 weeks. Group I (control) received 3 mL/kg olive oil intraperitoneal twice weekly in addition to feed and water ad libitum . Group II received CCl 4 3 mL/kg twice weekly. Groups III, IV and V received 100, 200 and 500 mg/kg wild edible P. tuber-regium mixed with feed by ingestion daily in addition to 3 mL/kg CCl 4 twice weekly, respectively. Group VI received 500 mg P. tuber-regium daily. Liver and body weights were recorded. Liver function tests, oxidative stress biomarkers, bilirubin, ascorbic acid and α-tocopherol were assayed. Histopathology of the liver was carried out. The gas chromatography-mass spectroscopy analysis yielded 10 antioxidants. Results CCl 4 increased the levels of alanine transaminase, aspartate transaminase, alkaline phosphatase, bilirubin and malondialdehyde from 24±1.778 iu/L, 53±3.7 iu/L, 257±19 iu/L, 0.45±0.03 mg/dL and 1.90±0.42 μmol/L in the control group to 48±2.5 iu/L, 81±2.10 iu/L, 495±38 iu/L, 1.20±0.09 mg/dL and 14.0±2.6 μmol/L in the treated group, respectively. Conclusions P. tuber-regium prevented the necrosis, edema and vein congestion observed in the CCl 4 -only group. P. tuber-regium is effective in protecting the liver against CCl 4 -induced damage.

Objectives The main objective of the present study is to evaluate the mitigative effect of hydroalcoholic extract of Momordica cymbalaria fruits against sodium fluoride (NaF) induced hepatotoxicity. Methods In this study, Wistar male albino rats were randomly divided into five groups of six rats each. Group I and II served as normal and toxic controls. Group III as plant control received extract at a dose of 400 mg/kg b. wt, p.o and Groups IV and V as treatment groups received extract at a dose 200 and 400 mg/kg b. wt, p.o for 30 days. All groups except Groups I and III received 100 ppm of NaF through drinking water. After completion of the study, blood collected for the estimation of liver blood serum biomarkers such as aspartate aminotransferases (AST), alanine aminotransferases (ALT), alkaline Phosphatase (ALP), direct and total bilirubin, total protein and albumin. The liver tissue homogenate was for estimation of lipid peroxidation, catalase, and reduced glutathione levels. Results The results showed that NaF intoxication caused elevation of liver blood serum levels and lipid peroxidation; decreased levels of serum total protein, albumin and liver reduced glutathione, and catalase observed. The treatment groups showed decreased elevated serum biomarkers (ALT, AST, and ALP), liver lipid peroxidation and increased serum total protein and albumin, liver reduced glutathione and catalase levels in a dose-dependent manner. Histopathological studies also further strongly supported for mitigative effects of the plant. Conclusions In conclusion, our findings of the study indicated that M. cymbalaria fruits were a potential drug candidate in the treatment of NaF induced hepatotoxicity.

Objectives Kaolinite clay is an abundant natural resource in Nigeria with several industrial applications. Incidentally, the wide-scale use of kaolinite clay is hampered by its small surface area. The objective of this study was to assess the effects of amine-modified clay on electrolyte, thyroid, and kidney function markers. Methods Modification of kaolinite clay with an amine functional group was achieved using surface grafting technique. Characterization with a scanning electron microscope and Brunauer-Emmett Teller surface area analyzer confirmed this modification. However, there is sparse information on the effect of amine-modified kaolinite clay on electrolyte homeostasis, thyroid, and renal function. Rats were administered amine-modified kaolinite clay at the doses of 1, 2, and 5 mg/kg body weight. Results After 14 days of repeated-dose treatment, there were no significant changes in levels of albumin, uric acid, triiodothyronine, thyroxine, ratio of triiodothyronine to thyroxine, and relative kidney organ weight. Furthermore, there were no changes in the concentration of potassium, although amine-modified kaolinite clay significantly decreased sodium, calcium, and total cholesterol levels. Amine-modified kaolinite clay, at all treatment doses, also preserved the renal histoarchitecture and oxidative balance in rats. Conclusions This study reports on the effect of amine-modified kaolinite clay on renal markers and thyroid function, and further deepens our understanding of their biochemical action. This baseline data may boost the prospect of using amine-modified kaolinite clay in the treatment of contaminated water.

Objectives Blend of seeds and leaves of Picralima nitida herein referred to as West African Durand powder (WDP) was investigated for antinociceptive and anti-inflammatory properties. Methods Acute toxic effect of the aqueous extract was evaluated in mice of both sexes. Antinociceptive effect of WDP (100–400 mg/kg) was evaluated in models of acetic acid-induced writhing and thermal nociception on hot plate in mice. Carrageenan-induced paw oedema and air pouch rat models were used to evaluate the anti-inflammatory activity of the extract. Results WDP (2,000 mg/kg) showed no toxic effect in mice. WDP at 100, 200 and 400 mg/kg inhibited abdominal writhings by 59.9, 66.0 and 79.0%, respectively. There was a significant increase in reaction time on the hot plate tests in mice treated with WDP (400 mg/kg). The paw oedema was reduced by WDP (100, 200 and 400 mg/kg) 5 h post-carrageeenan. Exudate volume was significantly reduced to 39.8 and 44.8% by 200 and 400 mg/kg WDP, respectively. WDP reduced Leucocytes counts (23.3 and 57.1%, respectively) and neutrophil counts (28.1 and 60.0%, as well as reduced nitrites, malondialdehyde levels and increased glutathione concentrations in the air pouch. Conclusions These results suggest that aqueous extract of blend of seeds and leaves of P. nitida possesses antinociceptive and anti-inflammatory properties.

Objectives Hypertension is the number one risk factor and primary contributor of cardiovascular diseases. Caesalpinia benthamiana is a valuable medicinal plant with unvalidated anti-hypertensive activity. This study was carried out to explore the antihypertensive effect of C. benthamiana on uninephrectomized hypertensive rats. Methods Fifty rats were grouped into five groups, each containing 10 animals: Group A-normal control (normotensive); B-uninephrectomized control; C-uninephrectomized treated with 50 mg/kg C. benthamiana extract; D-uninephrectomized treated with 100 mg/kg C. benthamiana ; and E- uninephrectomized treated with 10 mg/kg of Lisinopril. Results Significant increases were observed in systolic, diastolic and mean blood pressure of uninephrectomized control rats. Furthermore, markers of oxidative stress (malondialdehyde, hydrogen peroxide, protein carbonyl, myeloperoxidase and the advanced oxidative protein products) increased significantly while antioxidant status (reduced glutathione, glutathione peroxidase, glutathione S-transferase and superoxide dismutase), reduced significantly in uninephrectomized hypertensive rats. Histopathology revealed thrombosis and occlusion of coronary vessels in the heart, and congestion in the kidney. However, the observed high blood pressure parameters were remarkably normalized together with reduction in markers of oxidative stress and improvement in antioxidant defence system of uninephrectomized hypertensive rats treated with C. benthamiana extract similar to normotensive rats. Conclusions C. benthamiana extract exhibited antihypertensive action, strong antioxidant ability, attenuated oxidative stress-mediated hypertension and lessened the development of cardiac and renal damage associated with hypertension induced by uninephrectomy and high dietary intake of salt. Together, C. benthamiana extract might be useful in the management of hypertension due to volume overload in the cardiovascular system.

Objectives Cistus salviifoluis L. is a shrub from Cistaceae family used in many traditional medicines for the treatment of various diseases including diabetes mellitus. The aim of this study was to evaluate the in vivo antidiabetic potential of the aerial parts aqueous extract of Cistus salviifolius L. (CSA). Methods Experimental diabetes was induced in adult male mice by intra-peritoneal injection of Streptozotocin-nicotinamide (STZ-NC). CSA at a dose of 500 mg/kg was administered daily to the diabetic mice for four weeks. The effect of the extract on hyperglycemia, body weight, serum total cholesterol, triglycerides, hepatic and renal functional markers were determined. Histopathological examination of the mice pancreas was also performed. The diabetic animals treated with CSA were compared with animals treated by the standard drug metformin. Results Treatment with CSA showed a significant reduction in blood glucose, total triglycerides and creatinine levels and prevented the reduction of body weight caused by diabetes. Furthermore, histopathological analysis of the mice pancreas showed that the group treated with CSA reduced damage induced by STZ-NC on islets of Langerhans cells when compared to the diabetic control. Conclusions The results suggest that the aqueous extract of Moroccan C. salviifolius L. possesses beneficial effect on treatment of diabetes.

Background Urinary tract infections (UTIs) are the most common bacterial infection encountered worldwide and are associated with significant morbidity and mortality. Methods The present study was undertaken to investigate the biofilm-forming ability, antibiotic susceptibility patterns and extended spectrum β-lactamase (ESBL) production of seven uropathogenic isolates comprising both Escherichia coli and Klebsiella pneumoniae . The morphological, cultural and biochemical tests for the identification of the isolates, antibiotic susceptibility test, detection of ESBL production, biofilm formation on 96-well microtiter plate and Congo red agar (CRA) media are performed. Results The antimicrobial susceptibility profiles obtained in this study showed that the most active drugs gentamicin, amikacin and imipenem (100% sensitivity) were followed by amoxicillin-clavulanic acid (85% sensitivity), co-trimoxazole, ciprofloxacin (57% sensitivity) ceftazidime and kanamycin (50% sensitivity). All the isolates showed resistance to amoxicillin followed by ceftriaxone and cefotaxime (71% resistance), and the scenario gets more complicated because of the production of ESBL by five isolates (three E. coli isolates and two K. pneumoniae ). The strains were also able to form biofilm as tested on CRA medium and by microtiter plate assay. The correlation between ESBL, non-ESBL and biofilm-producing E. coli and K. pneumonia was determined along with the multiple drug resistance patterns of E. coli and K. pneumonia . Conclusions The findings of the study indicate that the emergence and rapid spread of such multidrug-resistant pathogens are of great concern. Early detection of ESBL-producing pathogen is of paramount clinical importance; therefore, strict infection control practices as well as therapeutic guidance for confirmed infection can be rapidly initiated.