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Introduction Exposure to stress during pregnancy has been shown to have adverse effects on pregnancy outcomes such as low birth weight, spontaneous abortion and premature delivery. Honey has been shown to improve testicular function in rats exposed to cigarette smoke. The aim of this study was to determine the effects of honey on corticosterone level, adrenal gland histomorphometry and pregnancy outcomes in pregnant rats subjected to restraint stress. Materials and methods Rat dams were divided into four groups ( n = 10/group), i.e. control, honey, stress and honey plus stress (honey + stress) groups. Rats from honey and honey + stress groups received Tualang honey (1.2 g/kg body weight/day) orally by gavage from Day 0 of pregnancy until delivery. Rats from stress and honey + stress groups were subjected to stress by repeated restraining (three times/day) from Day 11 of pregnancy until delivery. Following delivery, pregnancy outcomes were assessed and dams were euthanized at postnatal Day 21 for assessments on serum corticosterone level, adrenal gland histology and rate of resorption. Results Rats from stress group had significantly higher corticosterone level, zona fasciculata thickness and duration of pregnancy as well as decreased litter size when compared with control and honey groups. These parameters were significantly improved in rats receiving honey (honey + stress group). Conclusion Supplementation of honey has a protective effect against increased corticosterone level and zona fasciculata thickness as well as impaired pregnancy outcomes in rats subjected to restraint stress.

A major disadvantage that may occur in association with atorvastatin (ATV) therapy is elevation of serum transaminases. This study was designed to evaluate the effects of treatment of rats with various doses of ATV (2, 5, and 10 mg/kg/day) on liver function, oxidative stress, and histology and on the severity of acetaminophen (APAP) hepatotoxicity. ATV administration for 21 days resulted in a dose-dependent significant rise in serum activities of alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase. Only ATV at 10 mg/kg/day decreased reduced glutathione (GSH) levels and superoxide dismutase (SOD) activity, increased malondialdehyde (MDA) levels, and elicited histopathological changes in the liver. In rats challenged with APAP (500 mg/kg), the livers showed centrilobular necrosis with evident oxidative stress and liver dysfunction after 24 h. Rats challenged with APAP after pretreatment with ATV 2 or 5 mg/kg/day showed significantly lower activities of serum enzymes, higher hepatic GSH levels and SOD activities, lower MDA levels and milder histopathological changes compared with rats challenged with APAP after pretreatment with ATV 10 mg/kg/day or without drug pretreatment. In conclusion, the effect of ATV on the liver is dose dependent. Our results showed that ATV, at the highest dose used, induced hepatic lipid peroxidation and injury, suggesting a role for oxidative stress in ATV-induced hepatotoxicity. However, lower doses of ATV attenuated APAP-induced hepatotoxicity via a mechanism related, at least in part, to a reduction of APAP-induced hepatic oxidative stress. These results are of practical interest as both drugs may be used concurrently in clinical practice.

This study was undertaken to determine the phenolic compounds and the anti-atherogenic effect of bee bread in high-fat diet (HFD)-induced obese rats. The presence of phenolic compounds in bee bread was determined by liquid chromatography&ndash, mass spectrometry. Thirty-two male Sprague Dawley rats were divided into four groups, (n = 8/group), i.e., Normal (N), HFD (high-fat diet), HFD + BB (high-fat diet and 0.5 g/kg/day bee bread), and HFD + O (high-fat diet and 10 mg/kg/day orlistat) groups. After 6 weeks of the experiment, rats were sacrificed. Five phenolic compounds were identified in bee bread, namely, caffeic acid, ferulic acid, kaempferol, apigenin, and isorhamnetin. Bee bread significantly reduced Lee obesity index and levels of total cholesterol (TC), low-density lipoprotein (LDL), fatty acid synthase (FAS) activity, atherogenic index, oxidised-LDL (oxLDL), and malondialdehyde (MDA), and significantly increased aortic antioxidant activities, such as those of superoxide dismutase (SOD) and glutathione peroxidase (GPx). Adipocyte sizes were found to be smaller in the HFD + BB group compared to the N group, and en face aortas showed an absence of atherosclerotic plaque in rats supplemented with bee bread. These changes might suggest an anti-atherogenic effect of bee bread in HFD-induced obese rats via its antioxidant and hypocholesterolaemic properties.

Introduction: Obesity has been reported to impair male reproductive function and testicular apoptosis while bee bread has been traditionally consumed to enhance male fertility.Objective: The objective of this study was to determine the effects of Malaysian bee bread on apoptosis and proliferation of testicular germ cells in high-fat diet-induced obese rats.Methods: Twenty-four adult male Sprague Dawley rats weighing between 250-300 g were randomised into four groups (n=6/group), namely normal control (NC), high-fat diet (HFD), HFD plus bee bread (HFD+B) and HFD plus an anti-obesity drug orlistat (HFD+O) groups. Bee bread (0.5g/kg/day) and orlistat (10 mg/kg/day) were suspended in distilled water and given by oral gavage for 12 weeks. Markers for apoptosis and proliferation of testicular germ cells were assessed.Results: mRNA transcript levels of caspase-3, caspase-8, caspase-9, p53 and Bax/Bcl2 ratio in the testis of HFD group were significantly increased while immunohistochemical staining of cleaved caspase-3 increased and proliferating cell nuclear antigen (PCNA) immunoexpress ions decreased relative to NC group. Treatment with bee bread significantly decreased the apoptotic markers, significantly decreased mRNA transcript levels of anti-apoptotic markers (Bcl2) and increased PCNA immunoexpression in HFD+B, relative to NC group and HFD+O.Conclusion: Bee bread improved proliferation of testicular germ cells by attenuating apoptosis in high- fat diet-induced obese male rats.International Journal of Human and Health Sciences Supplementary Issue: 2019 Page: 44

Background We assessed histopathological changes of ovaries and uterus in female rats subjected to different jumping exercise intensities combined with honey supplementation at one g/kg body weight/day. Methods A total of 72 rats were divided into six groups, 12 rats in each: control (C), 20 and 80 jumps (20E, 80E), honey (H), and 20 and 80 jump with honey (20EH, 80EH). Results The endometrium was significantly thicker in the rats in H, 20EH and 80EH groups compared to C, 20E, and 80E. The myometrium thickness was significantly lower in 80E and significantly higher in 80EH compared to C, respectively. There was significantly higher myometrium thickness in 20EH and 80EH compared to 20E and 80E and H. The number of glands of the uterus in 20E and 80E was significantly lower than C. However, there was a significantly higher number of glands in H, 20EH, and 80EH compared to 20E and 80E. The numbers of uterus vessels were significantly lower in 80E compared to 20E. However, the numbers of vessels were significantly higher in H, 20EH, and 80EH compared to 80E. The number of ovarian haemorregia was significantly lower in 20E, 80E, H, 20EH, and 80EH compared to C. The number of corpora lutea was significantly lower in 80EH, H, 80E, and 20E compared to C. However, the number of corpora lutea was significantly higher in 20EH compared to J20 and H. Conclusion This study suggested that jumping exercises in particularly high-intensity exercise may induce histopathological changes in uterus and ovary in rats, and honey supplementation may ameliorate these effects.

ABSTRACT Background: Persistent hyperglycaemia results in complications in diabetes mellitus (DM) and metformin is the baseline drug used in diabetic management. The effect of metformin on fasting blood glucose (FBG), homogenized kidney tissue malonyldehyde (MDA), protein carbonyls (PCO), total antioxidant capacity (TAC) and histology in streptozotocin-induced diabetic rats was investigated. Methods: Eighteen Sprague Dawley rats were assigned into three groups (n= 6 rats per group i.e. A; negative control on distilled water, B; positive control on distilled water and C; on 100 mg/kg/day metformin groups. Diabetes mellitus (DM) was induced using streptozotocin 65 mg/kg intraperitoneally and treatments were given daily by oral gavage for 3 weeks. Plasma fasting blood glucose (FBG), kidney tissue oxidative stress markers and histology were determined. Results: The results showed that FBG, MDA, and PCO levels were significantly higher in B group compared to A group, and lower in C group compared to B. The TAC level was significantly lower in B compared to A and higher in C compared to B group of rats. However, though histological study shows improvement in kidney histology in all treatments, kidney weight did not differ. Conclution: The results suggest that, metformin reduces oxidative stress in streptozotocin-induced diabetic rats possibly through its antihyperglycaemic effect.

Introduction The effects of honey administration during normal pregnancy and prenatal stress on pain behavior in the offspring are not known. Here we examined the effects of Tualang honey administration during pregnancy and prenatal stress on pain responses in male rat offspring. Materials and methods Pregnant dams were divided into four groups; control (C), honey (H), stress (S) and stress with honey (SH). Tualang honey (1.2 g/kg) or distilled water was administered orally throughout pregnancy. S and SH groups were subjected to restraining stress from day 11 of pregnancy until delivery. Intraplantar formalin injection and thermal stimulus were given to the male adult offspring (220–300 g). Behavior data due to formalin injection and thermal stimuli were analyzed using repeated measures analysis of variance (ANOVA) and one way ANOVA respectively and significance level was taken as less than 0.05. Results The study showed that the offspring from the H group had higher tail flick latency time compared to C and offspring from SH group had a significant reduction in the formalin test score in phase 1 and late phase 2 compared to S group. Discussion The nutrients in Tualang honey are beneficial to support neural development of the fetus and capable to modulate the offspring's nociceptive responses. The present study provides novel knowledge regarding the possible role of Tualang honey in fetal neural development which modulates pain responses in later life. Further studies are required to elucidate the mechanisms of action of honey on pain behavior in the rat offspring.

Syzygium polyanthum(Wight) Walp. var.polyanthumleaves are consumed as a traditional Malay treatment of hypertension. This study investigates hypotensive potential of aqueous (AESP) and residual methanolic (met-AESP) extracts ofS. polyanthumleaves and possible involvement of autonomic receptors. AESP and met-AESP (20 to 100 mg/kg) were intravenously administered into anaesthetized Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Blood pressure and heart were monitored for 20 min. AESP and met-AESP induced significant dose-dependent hypotension, but only 100 mg/kg AESP caused mild bradycardia (n=5). AESP-induced hypotension was more potent than that of met-AESP in WKY. AESP has a faster onset time than that of met-AESP in both WKY and SHR. However, met-AESP-induced hypotension was more sustained than that of AESP in SHR. Blockages of autonomic ganglion andα-adrenergic receptors using hexamethonium and phentolamine (n=5for each group) partially attenuated AESP-induced hypotension, suggesting involvement ofα-adrenergic receptors. Blockages of autonomic ganglion,β-adrenergic, cholinergic receptors, and nitric oxide production using hexamethonium, propranolol, atropine, and N-ω-nitro-l arginine methyl ester (L-NAME) (n=5for each group) partially attenuated met-AESP-induced hypotension, suggesting involvement ofβ-adrenergic and cholinergic receptors via nitric oxide production.

Recently, numerous clustering methods have been tested and used in the segmentation process especially for medical imaging applications. The medical imaging analyses require high accuracy of result percentage. According to this issue, numerous studies have been carried out in medical imaging field such as segmentation technique. According to the high expectation of segmentation output, researchers have been attracted to study and develop new methods of segmentation techniques. Certain medical images can be classified as hard to process and understand. Therefore, several clustering algorithms have been proposed to meet the expectation from medical view as well as to produce better segmentation performance for medical images. In this study, the modified moving k-means algorithm is proposed for the segmentation problems. The objective of the modified moving k-means algorithm is to introduce the better technique of finding the nearest center for each pixel to be classified into different clusters. Then, the modified moving k-means algorithm is compared to the fuzzy c-means, k-means and moving k-means algorithms. The comparison result shows that the modified moving k-means algorithm produced better segmentation quality as compared to the other clustering techniques.

The aim of this study was to evaluate the effect of different doses of Malaysian honey on male reproductive parameters in adult rats. Thirty-two healthy adult male Sprague-Dawley rats were randomly divided into four groups (eight rats per group). Group 1 (control group) was given 0.5 ml of distilled water. Groups 2, 3 and 4 were given 0.2, 1.2 and 2.4 g kg(-1) body weight of honey respectively. The rats were treated orally by gavage once daily for 4 weeks. Honey did not significantly alter body and male reproductive organs weights. The rats in Group 3 which received honey at 1.2 g kg(-1) had significantly higher epididymal sperm count than those in Groups 1, 2 and 4. No significant differences were found for the percentage of abnormal sperm, elongated spermatid count, reproductive hormonal levels as well as the histology of the testis among the groups. In conclusion, Malaysian honey at a dose of 1.2 g kg(-1) daily significantly increased epididymal sperm count without affecting spermatid count and reproductive hormones. These findings might suggest that oral administration of honey at this dose for 4 weeks may enhance spermiogenesis in adult rats.

Background: Glycogen depletion and hypoglycemia have been associated with fatigue and decrement of performance during prolonged exercise Objectives: This study investigated the effectiveness of Acacia honey drink as a post-exercise recovery aid on glucose metabolism and subsequent running performance in the heat. Patients and Methods: Ten subjects participated in this randomized cross-over study. All subjects performed 2 trials. In each trial, all subjects went through a glycogen depletion phase (Run-1), 2-hour rehydration phase and time trial running phase (Run-2). In Run-1, subjects were required to run on a treadmill at 65% VO2max in the heat (31°C, 70% relative humidity) for 60 min. During 2-hour rehydration phase, subjects drank either plain water (PW) or honey drink (HD) with amount equivalent to 150% of body weight loss in 3 boluses (60%, 50% and 40% subsequently) at 0, 30 and 60 min. In Run-2, the longest distance covered in 20 min was recorded for determining running performance. Two-way repeated measured ANOVA and paired t-test were used for analysis. Results: Running distance in Run-2 covered by the subjects in the honey drink HD trial (3420 ± 350 m) was significantly (P < 0.01) longer compared to plain water PW trial (3120 ± 340 m). In general, plasma glucose, serum insulin and osmolality were significantly (P < 0.05) higher in HD compared to PW during the rehydration phase and Run-2. Conclusions: These findings indicate that rehydration with honey drink improves running performance and glucose metabolism compared to plain water in the heat. Thus, honey drink can be recommended for rehydration purpose for athletes who compete in the heat.

Melatonin's function in modulating the circadian cycle of Plasmodium falciparum has been an intense investigation for the past 45 years. The stimulatory effects of melatonin on malaria growth, development and differentiation have been confirmed by numerous studies conducted in the past 40 years but the molecular mechanisms underlying melatonin stimulatory effects have been well understood recently. Melatonin has been identified as a "signal" essential for synchronization of malaria parasitic cell cycle. Melatonin has been shown to modulate the release of intracellular Ca²⁺ and cAMP in Plasmodium falciparum. In this context, melatonin receptor blocking agent luzindole has been shown to block melatonin's actions in these intracellular events occurring in human malaria parasites. Recent studies have resulted in the synthesis and development of melatonin derivatives, compounds 7-11 and 12-16. Of these compounds 12, 13 and 14 were able to inhibit the Plasmodium falciparum growth and this serves as a promising lead for the development of future antimalarial compounds that will have rapid antimalarial actions with low toxicity. Some antimalarial drugs that have been patented are also summarized in this review.

Malaria, one of the most deadly diseases of our time, affects more than 200 million people across the globe and is responsible for about one million deaths annually. Besides Plasmodium falciparum which is the main cause for malarial infection in human beings, Plasmodium knowlesi from Malaysia also remains as the most virulent parasite spreading fast not only in Malaysia but also in different parts of the world. Global malaria eradication program by use of insecticide spraying has resulted in good response in the past. Treatment of malaria-infected patients with antimalarial drugs has helped to eliminate malarial infections successfully, but with increased resistance displayed by malarial parasites to these drugs, there is resurgence of malaria caused both by drug resistance and by infection caused by new malarial species like Plasmodium knowlesi. Recent advances on molecular studies on malarial parasites reveal that the pineal hormone melatonin acts as a cue for growth and development of Plasmodium falciparum. Same may be true for Plasmodium knowlesi also. Hence, treatment modalities that can effectively block the action of melatonin on Plasmodium species during nighttime by way of using either bright light therapy or use of melatonin receptor blocking can be considered as useful approaches for eliminating malarial infection in man.

Melatonin is a versatile molecule, synthesized mainly by the pineal gland and in small amounts by other organs like retina, gastrointestinal tract, thymus, bone marrow, and lymphocytes. Other than its important role in various body functions like sleep and circadian rhythm regulation, antioxidant functions, and control of reproductive functions, melatonin has been found to be effective in combating infections by various bacteria including chlamydia and Mycobacterium tuberculosis, as well as by viruses. Molecular mechanisms of antimicrobial actions of melatonin have been proposed to be due to its effects on free radical formation, direct regulation of bacterial duplication, and depletion of intracellular substrates like iron. It also has protective effect against sepsis as shown in various animal models of septic shock. This protective effect is suggested to be due to its antioxidant, immunomodulating, and inhibitory actions against the production and activation of pro-inflammatory mediators. Clinical studies have shown the potential beneficial use of melatonin in treating septic shock with severe respiratory distress syndrome and associated multiorgan failure in addition to its antimicrobial and antiviral actions.

The immune system of the body plays an important role in fighting against cancer and infectious diseases. The decreased immune function has been primarily attributed to the increased incidence of neoplastic and infectious diseases in the elderly. Alteration in circadian rhythmicity of various subsets of lymphocyte population in cancer patients suggests impaired integration of nervous, endocrine, and immune responses in neoplastic disease. The photoperiodic regulation of immune function with enhancement during short photoperiods and inhibition during long photoperiods is supported by the seasonal outbreak of some infectious diseases. The pineal biomolecule melatonin could be a very useful resource for inhibiting neoplastic growth as its immunomodulatory role may stimulate several immune mechanisms. Melatonin stimulates natural killer cells which are known to attack and destroy cancerous cells. It also influences T-helper 1 cells, B lymphocytes, and release of cytokines from immunoregulatory cells. The immunomodulatory role for melatonin and its application in the control of infectious and neoplastic diseases is supported by the synthesis of melatonin by lymphocytes and thymus.

Alzheimer’s disease (AD) is characterized by a progressive loss of memory and cognitive function as well as behavioral and sleep disturbances including insomnia. The pathophysiology of AD has been attributed to oxidative stress-induced amyloid β-protein (Aβ) deposition. Abnormal tau protein, mitochondrial dysfunction, and protein hyperphosphorylation have been demonstrated in neural tissues of AD patients. AD patients exhibit severe sleep-wake disturbances associated with rapid cognitive decline and memory impairment. Optimally effective management of AD patients requires a drug that can arrest Aβ-induced neurotoxic effects and restore the disturbed sleep-wake rhythm with improvement in sleep quality. In this context, the pineal hormone melatonin has been demonstrated to be an effective antioxidant that can prevent Aβ-induced neurotoxic effects through a variety of mechanisms. Sleep deprivation itself produces oxidative damage, impaired mitochondrial function, neurodegenerative inflammation, altered proteosomal processing, and abnormal activation of enzymes. Treating sleep disturbances is also necessary for preventing and arresting AD progression. Besides melatonin, use of melatonergic agonists such as ramelteon, agomelatine, and tasimelteon, which are now used clinically for treating insomnia and other sleep disorders, may also be beneficial in treating AD.

Background The effects of high and low jumping exercise intensities combined with honey on bone and gonadotrophins were investigated in eighty four 9 week-old female rats. Methods The experimental groups were 20 or 80 jumps per day combined with or without honey supplementation (HJ20, HJ80, J20 and J80), honey supplementation (H), sedentary without supplementation control (C), and baseline control (C0) groups. Results Study results showed that HJ80 elicited greatest beneficial effects on tibial and femoral mass, serum total calcium and alkaline phosphatase concentrations. There were significantly (p 20, J80 compared to C, with exception of HJ20 and HJ80. Serum luteinizing hormone concentrations were significantly (p 20, HJ80 and J20 compared to J80. Conclusions It appears that high intensity jumping exercise combined with honey supplementation resulted more discernable effects on bone. Meanwhile, honey may protect against the adverse effects induced by jumping exercise on gonadotropins in female rats.

Immune mechanism of the body plays an important role in arresting neoplastic growth and in controlling infectious diseases. The innate immunity, adaptive immunity comprising of cellular and humoral immunity have distinct roles in fighting against cancer and infectious diseases. The role of neutrophils, monocytes-macrophages, T helper (Th)-1 and Th-2 lymphocytes, B-lymphocytes and cytokines in arresting neoplastic growth and in combating infections and the complex interrelationship among themselves and with neuro-endocrine network in the body has gained much impetus with the discovery of number of receptors and binding surfaces on these cells. The increased incidence of neoplastic and infectious diseases seen in the elderly is attributed primarily to decreased immune function of the body, and termed as immunosenescence. Alteration in circadian rhythmicity of various subsets of lymphocyte population has been documented in the elderly. Similarly recent studies on cancer patients reveal that there exists two distinct types of lymphocytes with some cells exhibiting acrophase during morning and others in the night and circadian variation of lymphocyte population in cancer patients suggest impaired integration of nervous, endocrine and immune responses in neoplastic disease. Seasonal outbreak of some infectious diseases seen in some parts of the world has supported the photoperiodic regulation of immune function with enhancement during short photoperiods and inhibition during long photoperiods. Although the evidences for this are largely derived from animal studies, its application to human studies is still in a preliminary stage. However, the neurohormone melatonin which was shown to have an immunomodulatory role may stimulate immune mechanisms and in this way, melatonin could be a very useful resource for inhibiting neoplastic growth. Melatonin stimulates natural killer cells which are known to attack and destroy cancerous cells by their immunosurveillance mechanism. In addition, Th-1 cells, B-lymphocytes, release of cytokines from immunoregulatory cells are influenced by melatonin. The synthesis of melatonin by lymphocytes and thymus supports an immunomodulatory role for melatonin and its application in the control of infectious and neoplastic diseases. Fil: Srinivasan, Venkataramanujam. Medical Sciences Research Study Center. Sri Sathya Sai Medical Educational and Research Foundation; India Fil: Maestroni, George. University of Inubria; Italia Fil: Rosenstein, Ruth Estela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina Fil: Mohamed, Mahaneem. University Sains Malaysia; Malasia

The effect of cigarette smoke (CS) on histology of male accessory reproductive organs and the possible protective effect of honey supplementation in rats were investigated in this study. Rats received distilled water, honey, CS exposure or honey plus CS exposure. Honey (1.2 g/kg body weight/day) was administered by gavage and CS exposure (3 times per day) was done in a chamber for 13 weeks. CS exposure significantly increased relative weight of epididymis and ventral prostate. There were also significantly increased number of clear cells and epithelial height of cauda epididymis as well as severe interstitial oedema and decreased epithelial height of prostate gland. However, with the supplementation of honey, these histological changes were significantly reversed suggesting the protective effect of honey against the toxic effect of CS on male accessory reproductiveorgans in rats.

Malaria, one of the most deadly diseases of our time affects more than 200 million people across the globe and is responsible for about one million deaths annually. Until recently Plasmodium falciparum has been the main cause for malarial infection in human beings but now Plasmodium knowlesi from Malaysia remains as one of the most virulent parasite spreading fast not only in Malaysia but in different parts of the world. Hence there is urgent need for the global fight to control malaria. Global malaria eradication program by use of insecticide spraying has resulted in good response in the past. Treatment of malaria infected patients with anti-malarial drugs has helped to eliminate malarial infections successfully but with increased resistance displayed by malarial parasites to these drugs there is resurgence of malaria caused both by drug resistance as well as by infection caused by new malarial species like Plasmodium knowlesi. With recent advances on molecular studies on malarial parasites it is now clear that the pineal hormone melatonin acts as a cue for growth and development of Plasmodium falciparum. Same may be true for Plasmodium knowlesi also. Hence treatment modalities that can effectively block the action of melatonin on Plasmodium species during night time by way of using either bright light therapy or use of melatonin receptor blocking can be considered as useful approaches for eliminating malarial infection in man.

Malaria remains a global health problem affecting more than 515 million people all over the world including Malaysia. It is on the rise, even within unknown regions that previous to this were free of malaria. Although malaria eradication programs carried out by vector control programs are still effective, anti-malarial drugs are also used extensively for curtailing this disease. But resistance to the use of anti-malarial drugs is also increasing on a daily basis. With an increased understanding of mechanisms that cause growth, differentiation and development of malarial parasites in rodents and humans, new avenues of therapeutic approaches for controlling the growth, synchronization and development of malarial parasites are essential. Within this context, the recent discoveries related to IP3 interconnected signalling pathways, the release of Ca2+ from intracellular stores of Plasmodium, ubiquitin protease systems as a signalling pathway, and melatonin influencing the growth and differentiation of malarial parasites by its effects on these signalling pathways have opened new therapeutic avenues for arresting the growth and differentiation of malarial parasites. Indeed, the use of melatonin antagonist, luzindole, has inhibited the melatonin's effect on these signalling pathways and thereby has effectively reduced the growth and differentiation of malarial parasites. As Plasmodium has effective sensors which detect the nocturnal plasma melatonin concentrations, suppression of plasma melatonin levels with the use of bright light during the night or by anti-melatonergic drugs and by using anti-kinase drugs will help in eradicating malaria on a global level. A number of patients have been admitted with regards to the control and management of malarial growth. Patents related to the discovery of serpentine receptors on Plasmodium, essential for modulating intra parasitic melatonin levels, procedures for effective delivery of bright light to suppress plasma melatonin levels and thereby arresting the growth and elimination of malarial parasites from the blood of the host are all cited in the paper. The purpose of the paper is to highlight the importance of melatonin acting as a cue for Plasmodium faciparum growth and to discuss the ways of curbing the effects of melatonin on Plasmodium growth and for arresting its life cycle, as a method of eliminating the parasite from the host.

Cigarette smoking is associated with sexual dysfunction and impaired fertility in males. The aim of this study was to determine the potential protective effect of honey against the toxic effect of cigarette smoke (CS) on sexual behavior and fertility of male rats. Thirty-two adult Sprague-Dawley rats were randomly divided into four groups (8 rats/group) as control, honey (H), CS and H plus CS (H + CS) groups. Rats in control and CS groups received oral administration of distilled water daily while rats in H and H + CS groups received honey (1.2 g/kg body weight/day) by oral gavage. Rats in CS and H + CS groups were also exposed to CS for 8 min 3 times/day. From 10 to 13 weeks of treatment, each male rat was cohabited with 3 untreated female rats for sexual behavioral and reproductive performance studies. Honey significantly increased the percentages of rats achieving intromission and ejaculation as well as increased mating and fertility indexes of male rats exposed to CS. Thus, honey has a protective effect against CS-induced impaired sexual behavior and fertility in male rats.

Melatonin is a versatile molecule, synthesized not only by the pineal gland, but also in small amounts by many other organs like retina, gastrointestinal tract, thymus, bone marrow, lymphocytes etc. It plays an important role in various functions of the body like sleep and circadian rhythm regulation, immunoregulatory mechanism, free radical scavenger, antioxidant functions, oncostatic actions, control of reproductive functions, regulation of mood etc. Melatonin has also been found to be effective in combating various bacterial and viral infections. Its administration has been shown to be effective in controlling chlamydial infections, infections induced by Mycobacterium tuberculosis, and also in many viral infections. Molecular mechanisms of anti microbial actions of melatonin have suggested to be due to effects on free radical formation, direct regulation of duplication of bacteria, depletion of intracellular substrates like iron etc. Besides, it is effective in sepsis as demonstrated in various animal models of septic shock. Melatonin's protective action against sepsis is suggested to be due to its antioxidant, immunomodulating and inhibitory actions against the production and activation of pro-inflammatory mediators. Use of melatonin has been beneficial in treating premature infants suffering from severe respiratory distress syndrome and septic shock. It has a potential therapeutic value in treating septic shock and associated multi organ failure in critically ill patients in addition to its antimicrobial and antiviral actions. The patents related to melatonin's use for treatment of bacterial infections and its use in clinical disorders are included.

Cigarette smoke (CS) can cause testicular damage and we investigated the possible protective effect of honey against CS-induced testicular damage and oxidative stress in rats. CS exposure (8 min, 3 times daily) and honey supplementation (1.2 g/kg daily) were given for 13 weeks. Rats exposed to CS significantly had smaller seminiferous tubules diameter and epithelial height, lower Leydig cell count and increased percentage of tubules with germ cell loss. CS also produced increased lipid peroxidation (TBARS) and glutathione peroxidase (GPx) activity, as well as reduced total antioxidant status (TAS) and activities of superoxide dismutase (SOD) and catalase (CAT). However, supplementation of honey significantly reduced histological changes and TBARS level, increased TAS level, as well as significantly restored activities of GPx, SOD and CAT in rat testis. These findings may suggest that honey has a protective effect against damage and oxidative stress induced by CS in rat testis.

Background: In Africa many plants and plant products are used traditionally for the managements of diabetes mellitus or its complication. But, science based evidence on some of this product safety need to be establish. Objective: We determine the effect of the Ethanol leaves extract of Ficus glumosa on fasting blood glucose level and liver enzymes of diabetes (DM) treated rats. Methods: Thirty (30) adult rats weighing (190 – 220) grams of about 8 to 10 weeks of age were used for this study in a standard laboratory setting. The animals were randomly divided into six groups (n= 5 rats /group) and diabetes was induced using single dose of alloxan 150 mg/kg intraperitoneal (ip). Group 6 served as the control group receiving distilled water (5ml/kg) alone via intra-peritoneal route (ip), Group 1 (DM+Distil water), 2, 3, 4 and 5 were given treatments for 7 days. Distilled water 5ml/kg, 100mg/kg, 200mg/kg and 400mg/kg of Ficus glumosa ethanol leaves extracts respectively via intraperitoneal ip while, Group 5 (DM+Insulin) received insulin 6.0 iu/kg. Before and after treatments Fasting blood sugar levels were measured. Rats were sacrifice for the Serum liver enzymes and liver tissue for histological study after the treatments. Results: The 100mg/kg and 400mg/kg of Ethanol leave extract of Ficus glumosa significantly lowered fasting blood glucose level and 400mg/kg show elevation in liver enzymes and reveal altered hepatocyte architecture (interphase hepatitis) compared with the control group 6 and lower dosage treatment group (2 and 3). Conclusion: The results of these study reveal that Ficus glumosa possesses hypoglycemic effect and at higher dose of 400mg/kg/day have effect on liver enzymes in diabetes rat.

Objectives An imbalance of vasoconstrictor and vasodilator substances in the placenta has been postulated in the pathogenesis of pregnancy-induced hypertension (PIH). There is however little information available on the kallikrein-kinin system (KKS) in women with PIH. The aim of this study therefore was to determine tissue kallikrein and kininogen levels and their distribution patterns in fetoplacental tissues from both normotensive pregnant (NTP) women and women with PIH. Study design The study group consisted of 24 women, 12 of whom had normal pregnancies, while 12 had PIH. Portions of amnion, chorion laeve, placental plate chorion, fetal placenta and maternal placenta were dissected from each freshly delivered placenta. Tissue kallikrein (total, active and inactive) and kininogen levels were estimated using a synthetic chromogenic substrate, S-2266 and an enzyme immunoassay, respectively. The data were analysed using Mann–Whitney U and Kruskal–Wallis tests. Results No significant differences were found for total, active and inactive tissue kallikrein levels in all fetoplacental tissues between both groups. However, kininogen levels were found to be significantly lower in chorion laeve, placental plate chorion, fetal placenta and maternal placenta from women with PIH when compared to those in similar tissues from NTP women. Conclusion These findings suggest the presence of an abnormality in the kallikrein-kinin system in the placentas of women with PIH, which requires further study.

Infertility cases have shown increasing growth in recent years where approximately 40% of root causes of infertility cases are related to men. Researchers have shown that the sperm motility has significantly contributed towards infertility as compared to its concentration and morphology. However, existing technique has faced difficulties in segmenting motile sperm in the low contrast regions. The movements of the motile sperms that are normally fast further complicate the automated segmentation. In this paper, we present a new region-based adaptive thresholding technique that consists of four main stages. Pixels of the images are classified based on the intensity distribution and those pixels are grouped and processed separately. Multiple thresholds are generated based on the classified group to ensure objects in low contrast regions are segmented. In addition, the proposed method does not require external pre-processing tool or phase contrast accessories prior to the sperm segmentation. Our experimental evaluations show that the proposed method produces significant improvement from the existing technique with the average accuracy of 95.74%. The qualitative results also indicate that the proposed method is able to segment the motile sperms in the low contrast region. These results of sperm segmentation are in agreement with the quantitative measurement of non-uniformity where the proposed method attains lower non-uniformity with respect to the results achieved by the other method.

Metabolic syndrome (MetS) is characterised by symptoms of obesity, insulin resistance, hypertension, dyslipidemia and diabetes mellitus. The pathophysiological mechanisms involved in MetS are complex and involved dysregulation of many biochemical and physiological regulatory mechanisms of the body. Elevated levels of low density lipoproteins like VLDL, and LDL with reduction of HDL seen in patients with MetS contribute to atherogenic dyslipedemia. Melatonin has been suggested to be effective in improving MetS through its anti-hyperlipidemic action. Melatonin reduced both adiposity, and body weight in experimental animal studies and also attenuated weight gain and obesityinduced metabolic alterations and this effect of melatonin is attributed to its anti-oxidative effects. Melatonin administration has been shown to inhibit insulin release by acting through both MT1 and MT2 melatonin receptors present in pancreatic β-cells. Melatonin also increased insulin sensitivity and glucose tolerance in animals fed with either high fat or high sucrose diet. Melatonin exerts most of its beneficial actions by acting through MT1 and MT2 melatonin receptors present in various tissues of the body and some of the metabolic actions of melatonin have been blocked by melatonin antagonist like luzindole. Ramelteon, the newly available melatonin agonist will also have more promising role in the control of MetS. The numbers of patents are available with regard to treatment of MetS. Drug related to antidepressant fluoxetine is used for treatment of MetS (US Patent No. 2008001400450). Anti-oxidants like S-adenosyl-methionine, Vitamin E, and Vitamin C have been found beneficial in treating MetS (US Patent No. 8063024). Melatonin being a powerful Antioxidant will have a promising role in treating patients with metabolic syndrome.

Honey has been used since ancient times for its nutritional as well as curative properties. Tualang honey is collected from wild honey bees’ hives on Tualang trees found in the Malaysian rain forest. It has been used traditionally for the treatment of various diseases, where its therapeutic value has partly been related to its antioxidant properties. This study therefore assessed the colour intensity, total phenolic content, antioxidant activity and antiradical activity of gamma irradiated Tualang Honey. The colour intensity at ABS45O was 489.5 ± 1.7 mAU, total phenolic content was 251.7±7.9 mg gallic acid /Kg honey, total antioxidant activity by FRAP assay was 322.1±9.7 (μM Fe(II)) and the antiradical activity by DPPH assay was 41.30 ± 0.78 (% inhibition). The data confirms that the antioxidant properties of gamma irradiated Tualang honey are similar to other types of honeys reported in the literature.Key words: Tualang honey, Malaysia, Total antioxidant activity, Gamma radiation, Phenolic content, DPPH assay