Fibromyalgia is a chronic condition causing pain, stiffness, and tenderness of the muscles, tendons, and joints accompanied by sleep abnormalities, anxiety & depression, pathophysiologic mechanism remains unknown, no structural, inflammatory, metabolic or endocrine abnormality has been identified. Toxic heavy metal exposure such as aluminum, lead, mercury, cadmium, and mercury are recognized as being a major cause of many illnesses and also plays a large role in many psychological conditions such that occur in fibromyalgia and chronic fatigue syndrome. Trace metals are metals in extremely small quantities in cells and tissue. They are a necessary part of nutrition and physiology, furthermore, several studies reported the importance of calcium & magnesium in biological functions especially in nerve and muscle functions, insufficient serum level or imbalance of these elements in human tissues and body fluids, has been suggested as a contributing factor for the development of fibromyalgia. The main objective of this study is to estimate  & evaluate possible role of some toxic, non -essential heavy metals ( Cadmium & Lead ) and whether the  change of serum essential metals ( Zinc& copper ,Magnesium & Calcium  ) levels  which may be involved   as a possible causative factor in  patients with fibromyalgia Syndrome (FMS) and their deleterious effect, in a group of patients as compared to healthy control individuals This clinical study was performed on 31 patients (25 females and 6 males) with age range of (40–65) years attending Rheumatology department / Baghdad Teaching Hospital / Iraq  and 21 healthy individuals ,  who were age and sex matched  were included in the study as control group . All patients diagnosed as having primary fibromyalgia syndrome (FMS) fulfill the criteria of the American College of Rheumatology (ACR) of FMS, in which whole blood levels of heavy metals for lead & cadmium, serum trace elements (zinc & copper) levels were measured in toxicological department laboratory, using Atomic Absorption spectrometry, while serum levels of calcium & magnesium were measured by traditional spectrophotometric methods. Fibromyalgia tender points and accompanying symptoms (fatigue, sleep disorders, headache, severity of pain and fatigue, and ability to perform daily activities were estimated by using clinical interview to fill Revised Fibromyalgia impact questionnaire (FIQR) was used for diagnosis & functional assessment, Statistical testing was carried by Student‘s t-test; All results were expressed as mean ± SD, P < 0.05 was considered statistically significant. For heavy metals, The results of this study found that there is a significant difference as elevation of blood lead (Pb) and cadmium (Cd) levels. On the other hand, Serum levels of essential metals show that, zinc (Zn) is significantly decreased in FMS patients group, Whereas there is a significant elevation in copper (Cu) of FMS Patients group compared to control group, whereas Serum levels of calcium (Ca) & magnesium (Mg) is significantly reduced in FMS Patients group compared to control group where (P<0.05) is considered significant. Conclusion from the study results, showed that there is significant disturbances and imbalance of essential & non-essential metals level, in FMS patients, that could be contributed to the pathogenesis of fibromyalgia syndrome, this may be based on mimicry metal theory, affecting certain trace metal -catalyzed antioxidant enzymes leading to some neurological signs of fibromyalgia.

Discovery of Bioactive compounds from marine sources especially fishes have always been of great importance since several decades and it is much more essential to identify novel natural products which might possess significant properties to treat various diseases. The main objective of this study is to evaluate the in vitro antibacterial, antifungal and larvicidal activities of various crude tissue extracts of the puffer fish Takifugu oblongus collected from the South – East Coast of India. The amount of protein present in each tissue was determined by spectrophotometric methods. The in vitro antibacterial and antifungal activities of the tissue extracts against various bacterial and fungal pathogens were investigated by well diffusion method. Larvicidal activity of the tissue extracts was assessed by analyzing the mortality rate of all tested larvae. Muscle extract showed highest protein content (340 µg/ml), whilst gonads extract showed least protein concentration (94 µg/ml) in the puffer fish. The measured zones of inhibition of various pathogens by different tissue extracts proved that gonads extract possessed highly commendable antibacterial activity against most bacterial strains. And muscle extract recorded lowest antibacterial activity. No antifungal activity was observed with all the tissue extracts. Though all the tissue extracts produced significant larvicidal activities, maximum activity was noticed with skin extract, whereas muscle extract showed the least. The crude tissue extracts of the puffer fish Takifugu oblongus showed noteworthy bioactivities and so further studies may be recommended to identify the natural bioactive compounds, so that they could be promising candidates for drug development.

Modulatory effect of the insecticide thiamethoxam (TMX) on biochemical and hormonal parameters, as well as histological structure was investigated. For this purpose twenty adult male Wistar rats were randomly and equally divided into two groups. The first group were treated orally with TMX by gavage at dose of 100 mg/kg bw, while the second group served as control. Treated animals received TMX once daily for 7 consecutive days. There is a significant elevation in the activities of AST, ALP, GGT, LDH, acid phosphatase and prostatic acid phosphatase in the serum of the TMX-intoxicated rats. On the contrary, the activities of ALT, PON-1, and AchE were decreased. The concentration of creatinine was increased, while the concentration of thyroxine hormone was decreased. Hydropic degeneration in hepatocytes, hyaline casts in the lumen of renal tubules, sharp edge outlines vacuoles in the sarcoplasm of the degenerated cardio-myocytes, and depletion in germinal epithelium of semineferous tubules were the major histopathological alterations detected in intoxicated rats.TMX exposure was not only associated with pronounced deleterious effects on the hepatic, renal, cardiac and testicular functions, but also the disruption in the activity of thyroid gland.

The aim of the present study was to evaluate the effect of methanolic extract (MSD) and flavonoid-rich extract (FSD) of Synsepalum dulcificum on alterations of hematological and electrolyte parameters in type 2 diabetic rats. A total of 63 animals were randomly distributed into nine groups of seven animals per group. Type 2 diabetes was induced in experimental animals by intraperitoneal injection of 40 mg/kg streptozotocin after administration of 10% fructose in their drinking water for 14 days. After confirmation of diabetes, treatment was continued for 21 days. At the end of the study hemoglobin (Hb) level, red blood cell count (RBC), packed cell volume (PCV), white blood cell count (WBC) and neutrophils were evaluated. Furthermore, serum levels of potassium (K⁺), calcium (Ca²⁺) and sodium (Na⁺) were also investigated. Results showed that a significantly (p < 0.05) higher Hb, PCV and RBC were observed in the MSD and FSD treated groups. However, a significantly (p < 0.05) lower WBC was observed in the extract treated groups when compared with the diabetic control. Furthermore, treatment with extracts also showed a significantly (p < 0.05) lower electrolyte levels than the diabetic control. It was evident that both MSD and FSD have the potential to improve the imbalances in hematological and electrolyte levels associated with type 2 diabetes as observed in this study. Therefore, the extracts could be considered relevant in the management of the disease.

Obesity is a significant risk factor for increased morbidity and mortality from cardiovascular disease and diabetes and it is also associated with many other medical conditions including cancer, liver and kidney diseases, sleep apnea, and depression. The inhibition of dietary fat absorption is a logical target for managing obesity and pancreatic lipase is a key enzyme involved in triglyceride absorption in the small intestine. Inhibitors of intestine lipases are suggested to function as antiobesity agents. Recently, studies have been intensified for new lipase inhibitors in natural resources with minimal adverse effect. In this view, attempts are made in the present study to evaluate antiobesity, antioxidant and anti-inflammatory activities of four medicinal plants namely Acorus calamus, Alpinia galanga, Cinnamomum zeylanicum and Piper cubeba. From the results obtained, it can be concluded that total phenol content was more in Piper cubeba, lipase inhibitory activity was high in Acorus calamus, DPPH radical scavenging activity was more in Cinnamomum zeylanicum, inhibition of lipid peroxidation and stabilization of RBC membrane was maximum for the extract of Alpinia galanga. Hence, preparation of herbal formulation using the investigated plant drugs will leads to the development of effective anti-obese drug.

The importance of studying the toxicity effects of methanolic extracts of Raphia hookeri on the survival of Clarias gariepinus cannot be over-emphasized, because they are mostly used locally for catching of fishes, because of its ichthyotoxic properties. These extracts end up killing excess fishes; including fingerlings, fry, sub-adults and adults, which could end up making the fish population unsustainable on the long run. This study will help to sensitize the fishermen over the long term effects of methanolic extracts of R. hookeri on fish population. 25 fingerlings of C. gariepinus were exposed to methanolic extracts of R. hookeri in concentrations of 0.00 (control), 30.0, 50.0, 70.0 and 100.0ppm for 96 hrs. All experiments were set up in triplicates. The C. gariepinus fingerlings exposed to different concentrations of methanolic extracts of R. hookeri exhibited signs of stress and erratic movement. All the time-effect relationship was found to be concentration dependent. A log-concentration probit regression analysis was significant (p<0.05), yielding a co-efficient of determination, r² of 0.913. The 96 hours LC₅₀ and 95% confidence limits for C. gariepinus exposed to different concentrations of Methanolic extract of R. hookeri was 1.70 ± 0.25ppm, having an interval of 10.15 – 2.0.077ppm. In conclusion, the study revealed that extracts of R. hookeri has cytotoxic and ichthyotoxic properties on the fingerlings of C. gariepinus.

A free radical is a molecule or molecular fragments containing one or more unpaired electrons in its outermost atomic or molecular orbit, and they are very reactive, capable of independent existence. Free radicals are well documented for playing a dual role in our body as both deleterious and beneficial species. Minerals are inorganic substance required by the body in small amount for a variety of function. The present study was designed to investigate the toxicity of free radicals on Drosophila melanogaster and free radicals scavenging activity of minerals which is most essential for routine metabolism. Minerals and free radicals effect on drosophila growth, body weight and longevity changes, free radicals scavenging activity assay were evaluated. The present study results reveal that addition of minerals enhances the growth and survival. Test organisms exposed to an array of concentrations of DPPH showed statistically significant eclosion inhibition from 10µM to 250 µM and 100% inhibition was observed in 500 µM. This study results enlightened the biological significance of free radicals in living organism’s physiology and maintenance.

Rheumatoid Arthritis (RA) causes damage to the joints that are affected by chronic inflammatory diseases. The aim of present study the anti-inflammatory effect of ethanolic extract Beta-beta wood (Lunasia amara Blanco.) in Complete Freund’s Adjuvant (FCA)-induced arthritis in mice. The ethanolic extract of L. amara (ELA) was orally administered once daily for 60 days after sub-plantar hind paw administration with CFA.  The ability of the plant extract to reduce swelling as a sign of arthritic inflammation was assessed of volume of hind paw swelling. Tumor necrosis alpha (TNF-α), interleukin 6 (IL-6) and paw histopathology were also determined.  The administration of ELA (50; 100, and 250 mg/kg BW) significant reduced volume of edema in mice-treated CFA (P<0.05) and the activity were equal to diclofenac sodium, 2 mg/kg BW. The reduction of edema were last until day 60. The administration of ELA was also significantly decreased the level of serum TNF-α and IL-6 in arthritis model in mice (P<0.05), but still less than diclofenac sodium. Histopathological examination indicated that ELA decrease edema and infiltration of inflammatory cells and synovial hyperplasia as well as protected joint destruction without osteoclast. The result suggests that ethanolic extract of L. amara might be beneficial for the treatment of chronic inflammatory disorder like rheumatoid arthritis.

The study of the toxicological and histopathological changes of Clarias gariepinus fingerlings exposed to different concentrations of cypermethrin is of great importance due to the fact that it helps reveal the extent of toxicological damages of cypermethrin on fishes. Cypermethrin is globally used for control of pest, but it is washed along with run-offs into the aquatic ecosystem, and this has an effect on the non-target species, thereby killing various fauna within the aquatic eco-system. Ten (10) fingerlings of Clarias gariepinus were introduced into each aquarium containing twenty (20) litres of water with 25ppm, 50ppm, 75ppm, 100ppm, 125ppm and 0.0ppm (Control) concentrations of cypermethrin and its effects were observed for 96hrs. The Clarias gariepinus fingerlings exposed to different concentrations of cypermethrin exhibited signs of stress and erratic movement. All the time-effect relationship was found to be concentration dependent. The fingerlings of Clarias gariepinus showed normal gill lamella, erosion of secondary gill lamella and haemorrhage of secondary gill lamella in the gill tissues when exposed to different concentrations of cypermethrin. The fingerlings exposed to the cypermethrin showed normal distribution hepatocytes, hyperplastic hepatic cells necrosis of hepatic cells in the liver tissues. A log concentration probit regression analysis was significant (p<0.05) yielding a co-efficient of determination, r² of 0.973 and having a 96 hours LC₅₀ with 95% confidence value of 1.80±0.28ppm. The study revealed that cypermethrin has toxicological and histopathological effects on different organs of Clarias gariepinus fingerlings.

Depression is a heterogeneous mood disorder that has been classified and treated in variety of ways. Although a number of synthetic drugs are being used as standard treatment for clinically depressed patient, the adverse effects compromise the therapeutic outcome. In the traditional systems of medicine, many plants and formulations have been used to treat depression for thousands of years. Solanum surattense is a commonly available plant throughout India and it has been claimed in traditional literature to be valuable plant against a wide variety of diseases. Till date no scientific data was available on the antidepressant activity of this plant. So, the present study was undertaken to investigate the effect of Solanum surattense (Family: Solanaceae), on depression in mice using tail suspension test (TST) and forced swim test (FST). Alcoholic and chloroform extract (50 and100 mg/kg p.o.) of S. surattense administered orally for 14 successive days had decreased the immobility periods significantly in a dose-dependent manner in both TST and FST, showing significant antidepressant-like activity. The activities of the extracts were found to be comparable to imipramine in both FST and TST. The results of this study indicate the potential for use of SS as an adjuvant in the treatment of depression.

The essential oil of the Santolina chamaecyparissus was isolated by herdro distillation using a modified Clevenger apparatus, and its constituents were identified and quantified by GC/MS analyses. The total composition of the essential oil was 92.09%. The main constituents of the essential oil were Artemisia ketone (15.65%). Another compounds present are as follow: Alpha-Amorphene (12.11%), Beta -Phellandrene (10.63%), Beta-Myrcene (7.42%), Nootkatone (6.97%). This study seeks to evaluate the chemical composition and its effect on the growth inhibition of microorganisms. The antibacterial was investigated in vitro against four gram-positive bacteria (Bacillus subitus, Staphylococcus aureus, Streptococcus pyogenes, Micrococus luteus) and six gram-negative bacteria (Escherichia coli, Salmonella typhimurium, Pseudomonas aeruginose, Klebsellia pneumonia, Proteus vulgaris, Vibrio parahaemolyticus), also against six fungi (Fusarium solani, Aspergillus flavus, Penecillium variable, Mucor sp, Rhyzopus sp and Candida albicans). The tested essential oil had different degrees of antibacterial and antifungal activity. The antimicrobial activities of essential oil evaluated in the present study by measuring the inhibition zones using Agar Disk Diffusion method. MIC and MBC varied from 0.4 – 1.6 mg/ml, and from 0.8 – 3.2 mg/ml, respectively, while MIC and MFC ranged from 0.4 to 3.2 and from 0.8 to 6.4 mg/ml respectively.

Diabetes mellitus (DM) is a metabolic disorder in which the carbohydrate and lipid metabolism is improperly regulated by insulin. Diabetes has been recognized to be one of highly risk independent factor for cardiovascular disorders, cardiomyopathy, coronary heart disease, congestive heart failure, peripheral arterial disease and stroke. Pomegranate considers a native fruit of Al-Taif region. Pomegranates contain numerous of antioxidant polyphenolic substances as compared to other fruits and vegetables. Polyphenols have been shown to be cardio protective in different model systems. The present study has been designed to demonstrate the protective effects of pomegranate peel extract against diabetic heart complications in streptozotocin (STZ)-induced diabetic rats. Method: Sixty adult male albino rats weighing 250 – 300 gm, were used in this study and divided into three groups; the first group, normal group; the second was subjected to induction of diabetes; the third group was treated with pomegranate extract orally. At the end of the trial (8 weeks), animals heart specimens were taken after the last injection and processed for histological and ultrastructural studies. Results: Biochemical studies showed increased values of glucose, and cardiac enzymes (Troponin I and CK-MB) and myoglobin in the second group while in the third group there was improvement in values of the examined parameters. Histopathological studies revealed obvious many degenerative changes that were varying from vacuolation to myocytolysis and loss of myofibrils. Ultrastructural examination showed extensive degeneration of the muscle fibers with marked loss and even complete disappearance of myofibrils, with degeneration of many mitochondria. The toxic effects of diabetes on the myocardium were markedly attenuated by pomegranate extract administration in combination with streptozotocin-induced diabetic injections. Conclusion: From this study, it was concluded that, pomegranate peel extract administration markedly attenuated diabetes induced cardiomyopathic changes.

Arsenic (As) is an important toxicant in environmental contamination. Residents with high as exposure demonstrated CKD or renal insufficiency, increased oxidative stress, also increased diabetes mellitus, cardiovascular disease and cancer. We aimed to examine the association between increased as exposure with cardiovascular risk factors in a sample of 209 residents of the As-contaminated villages of Uthai Thani Province in Thailand. Residents with high as exposure demonstrated significantly higher glucose, uric acid, microalbuminuria (MA), triglyceride (TG) levels, TG/high density lipoprotein- cholesterol (HDL-C) ratio and reduced HDL-C levels (p<0.05). In bivariate correlation, urinary as was significantly correlated with TG, HDL-C, TG/HDL-C ratio and MA levels. Overall findings showed that elevated urinary as appeared to increase risk of elevated TG/HDL-C ratio, elevated MA, elevated NAG, and reduced TAC; ORs and 95% CIs were 8.02 (2.75-23.40), 5.91 (2.24-15.61), 7.03 (2.73-18.09), and 9.23 (6.24-0.0001), respectively, after adjusting for BMI, age and sex. Our study revealed that elevated as exposure induces increased oxidative stress concomitant with CKD and associated with increased cardiovascular risk factors. These might be increased in morbidity and mortality from all degenerative diseases in the future.

Objective: The study aimed to determine the in vitro inhibitory activity of Abutilon indicum (Linn 1836) root extract on α-amylase and α-glucosidase enzymes for the prevention of diabetes, one of the major causes of mortality in the Philippines. Methods: This study utilized soxhlation with 95% ethyl alcohol for the extraction method. Three different concentrations (20 µg/ml, 40 µg/ml and 80 µg/ml) of Abutilon indicum root extracts were prepared. Root extracts, of varying concentrations, were subjected to inhibitory assay for a – amylase and a – glucosidase and quantified using a UV – VIS Spectrophotometer. Absorbance reading was measured at 540 nm and 405 nm for the a– amylase and the a– glucosidase inhibitory assay, respectively. Results: There was a dose-dependent percent inhibition by the extract against α-amylase (8.84% – 26.51%) and α-glucosidase (8.12% – 24.36%). Logarithmic regression analysis revealed the median inhibitory concentration (IC₅₀) of a – amylase (191.64 µg/ml) and a – glucosidase (207.13 µg/ml) with a potency and preference for α-amylase over α-glucosidase inhibition by the A. indicum root extract. Conclusion: The findings suggest that Abutilon indicum root extracts are inhibitors of a – amylase and a – glucosidase enzymes which possibly help reduce postprandial glucose levels.

Docetaxel (DTX) is one of the most effective chemotherapeutic agents in the treatment of breast cancer. Unfortunately, there is altered response to DTX due to resistance. DNA methylation, an epigenetic event, plays a vital role in cancer and chemotherapy drug resistance. Exploiting the gene reactivation by using epigenetically acting agents in combination with cytotoxic therapies, is a strategy of huge clinical relevance. Decitabine (DEC) is one such epigenetic drug. It has low oral bioavailability (4-5%) due to rapid degradation in acidic conditions and metabolism by cytidine deaminase in the liver and is therefore administered in clinical settings as i.v. infusion. In spite of the numerous advantages of oral chemotherapy, there is no conveniently administrable oral dosage form available for DEC. Since PLGA has an advantage of overcoming acidic and enzymatic degradation, the present investigation was aimed at fabricating PLGA 50:50 nanoparticles of decitabine (DEC-NPs); and thereafter, examine a combination treatment in vitro and in vivo with docetaxel (DTX). DEC-NPs were formulated by spontaneous emulsification solvent diffusion technique. The optimized formulation had PS of 124.3 ± 4.2 nm, ZP of -23.2 ± 1.2 mV, and EE of 41.8 ± 4.3%. A comparative study indicated that the cytotoxicity of DTX and DEC combination on MCF-7 cells was significantly higher (p <0.05) than DTX and DEC alone. Furthermore, cell uptake studies in Caco-2 cells, evidenced enhanced uptake of DEC-NPs in comparison to DEC. For in vivo studies, 8week old female SD rats were used and induced mammary tumour with 2 oral doses of DMBA in olive oil; 40 and 20 mg/kg. The results demonstrated that the combination of DEC and DEC-NPs with DTX significantly improved (p <0.05) the tumour response rate, significantly reduced (p <0.05) the tumour weight and volume when compared to single agents DTX or DEC. Treatment groups with DEC-NPs also displayed better response, as compared to DEC. The study proves that DEC and DEC-NPs enhance the anticancer potential of DTX.

The impossibility of eradicating the reason of recurrence of common bacterial diseases is our impetus in this study. Recent studies proved that this recurrence is caused by a subpopulation of bacteria, called the persisters, which is not susceptible with any antibiotic treatment because of its quasi-dormant state. Bacterial cellular processes are completely shut down but it thrives with cellular respiration and translation – making it possible for aminoglycoside antibiotics to target the ribosome. However, aminoglycosides have weak bactericidal activity and is energy dependent. The addition of sugar acts as the intermediate metabolite and produce energy to increase aminoglycoside uptake through proton motive force. As aminoglycoside uptake is increased, the eradication of the bacterial cell also increased. Different combinations of aminoglycoside and sugar metabolites were added to assayed bacterial persisters and spotted in a Luria-Bertani Agar to determine the number of colonies and its colony forming unit. The Escherichia coli persisters have the highest number of colonies which increases proportionally with time, while E. coli persisters with metabolite – aminoglycoside combination has a decreasing number of colonies as time increases. Galactose – gentamicin combination has the least number of colonies formed, with 7, 2, 0 and 0 for the first, second, third and fourth hour, respectively. The combination of galactose with gentamicin resulted to a decrease of active bacterial cells and decrease of persister viability as contact time increases. Therefore, Galactose – gentamicin combination is the best option for effective eradication of E. coli persisters via metabolic stimulation.