Months Of Oral Administration Research Articles

Prospective evaluation of ethambutol toxic optic neuropathy in patients of pulmonary tuberculosis

AimThe aim of the study was to evaluate visual parameters for early detection of ethambutol toxicity to prevent irreversible optic nerve damage. MethodThis cohort study included 50 newly diagnosed cases of pulmonary tuberculosis, i.e. 100 eyes, in people aged 18–72 years, who received ethambutol as part of the antitubercular therapy. Before starting antitubercular treatment, at each monthly visit, ophthalmic examination was done that included best corrected visual acuity, optic disc evaluation, colour vision, contrast sensitivity, pupil cycle time and automated perimetry for a period of six months. Ethambutol was discontinued in patients who showed signs of visual impairment. These patients were observed for another three months for reversibility of toxicity. ResultsVisual functions were normal in all patients at baseline. Out of 50 patients, 47 didn't show any signs of deterioration in visual functions even after six months of oral administration of ethambutol. However, 3 out of 50 patients, i.e. 6 eyes (6 %), showed signs of toxicity after 4–5 months – LogMAR visual acuity deteriorated from 0.00 to 1.08 (±0.40); mean contrast sensitivity deteriorated from 1.725 (±0.075) to 1.12 (±0.18); mean deviation in visual fields got impaired from −1.37 (±0.15) to −10.93 (±2.66); and colour vision got severely affected. All the affected patients were aged above 65. ConclusionIn the present study, six percent of 50 patients showed ethambutol toxic optic neuropathy. It was concluded that patients should be comprehensively evaluated for visual parameters before starting the ethambutol treatment. They should be closely monitored by an ophthalmologist for visual functions every month to detect ethambutol toxicity at the early reversible stage to prevent irreversible damage to the optic nerve. Patients should be asked to report immediately if they detect any blurring of vision or colour vision abnormality.

Myogenesis Effects of RGX365 to Improve Skeletal Muscle Atrophy.

Age-related skeletal muscle atrophy and weakness not only reduce the quality of life of those afflicted, but also worsen the prognosis of underlying diseases. We evaluated the effect of RGX365, a protopanaxatriol-type rare ginsenoside mixture, on improving skeletal muscle atrophy. We investigated the myogenic effect of RGX365 on mouse myoblast cells (C2C12) and dexamethasone (10 µM)-induced atrophy of differentiated C2C12. RGX365-treated myotube diameters and myosin heavy chain (MyHC) expression levels were analyzed using immunofluorescence. We evaluated the myogenic effects of RGX365 in aging sarcopenic mice. RGX365 increased myoblast differentiation and MyHC expression, and attenuated the muscle atrophy-inducing F-box (Atrogin-1) and muscle RING finger 1 (MuRF1) expression. Notably, one month of oral administration of RGX365 to 23-month-old sarcopenic mice improved muscle fiber size and the expression of skeletal muscle regeneration-associated molecules. In conclusion, rare ginsenosides, agonists of steroid receptors, can ameliorate skeletal muscle atrophy during long-term administration.

Improvement of Antialveolar echinococcosis efficacy of novel Albendazole-Bile acids Derivatives with Enhanced Oral Bioavailability.

Alveolar echinococcosis (AE) is a chronic and fatal infectious parasitic disease, which has not been well-researched. Current recommended therapies for AE by the World Health Organization include complete removal of the infected tissue followed by two years of albendazole (ABZ), administered orally, which is the only effective first-line anti-AE drug. Unfortunately, in most cases, complete resection of AE lesions is impossible, requiring ABZ administration for even longer periods. Only one-third of patients experienced complete remission or cure with such treatments, primarily due to ABZ's low solubility and low bioavailability. To improve ABZ bioavailability, albendazole bile acid derivative (ABZ-BA) has been designed and synthesized. Its structure was identified by mass spectrometry and nuclear magnetic resonance. Its physicochemical properties were evaluated by wide-angle X-ray diffraction, differential scanning calorimetry, scanning electron microscopy, and polarizing microscopy; it was compared with ABZ to assess its solubilization mechanism at the molecular level. To avoid the effects of bile acid on the efficacy of albendazole, the inhibitory effect of ABZ-BA on protoscolex (PSCs)s was observed in vitro. The inhibitory effect of ABZ-BA on PSCs was evaluated by survival rate, ultrastructural changes, and the expression of key cytokines during PSC apoptosis. The results showed that ABZ-BA with 4-amino-1-butanol as a linker was successfully prepared. Physicochemical characterization demonstrated that the molecular arrangement of ABZ-BA presents a short-range disordered amorphous state, which changes the drug morphology compared with crystalline ABZ. The equilibrium solubility of ABZ-BA was 4-fold higher than ABZ in vitro. ABZ-BA relative bioavailability (Frel) in Sprague-Dawley (SD) rats was 26-fold higher than ABZ in vivo. The inhibitory effect of ABZ-BA on PSCs was identical to that of ABZ, indicating that adding bile acid did not affect the efficacy of anti-echinococcosis. In the pharmacodynamics study, it was found that the ABZ-BA group had 2.7-fold greater than that of Albenda after 1 month of oral administration. The relative bioavailability of ABZ-BA is significantly better than ABZ due to the transformation of the physical state from a crystalline state to an amorphous state. Furthermore, sodium-dependent bile acid transporter (ASBT) expressed in the apical small intestine has a synergistic effect through the effective transport of bile acids. Therefore, we concluded that the NC formulation could potentially be developed to improve anti-AE drug therapy.

Effective management of atherosclerosis progress and hyperlipidemia with nattokinase: A clinical study with 1,062 participants.

Nattokinase (NK), known as a potent fibrinolytic and antithrombotic agent, has been shown to have antiatherosclerotic and lipid-lowering effects. However, data on human clinical studies are limited. In this clinical study involving 1,062 participants, our objective was to examine the efficacy of NK in atherosclerosis and hyperlipidemia and safety at the dose of 10,800 FU/day after 12 months of oral administration. Various factors, including lower doses that influence NK pharmacological actions, were also investigated. We found that NK at a dose of 10,800 FU/day effectively managed the progression of atherosclerosis and hyperlipidemia with a significant improvement in the lipid profile. A significant reduction in the thickness of the carotid artery intima-media and the size of the carotid plaque was observed. The improvement rates ranged from 66.5 to 95.4%. NK was found to be ineffective in lowering lipids and suppressing atherosclerosis progression at a dose of 3,600 FU/day. The lipid-lowering effect of NK was more prominent in subjects who smoked, drank alcohol, and subjects with higher BMI. Regular exercise further improved the effects of NK. Co-administration of vitamin K2 and aspirin with NK produced a synergetic effect. No noticeable adverse effects associated with the use of NK were recorded. In conclusion, our data demonstrate that atherosclerosis progression and hyperlipidemia can be effectively managed with NK at a dose of 10,800 FU/day. The lower dose of 3,600 FU per day is ineffective. The dose of 10,800 FU/day is safe and well tolerated. Some lifestyle factors and the coadministration of vitamin K2 and aspirin lead to improved outcomes in the use of NK. Our findings provide clinical evidence on the effective dose of NK in the management of cardiovascular disease and challenge the recommended dose of 2,000 FU per day.

EFFECT OF ORAL SUPPLEMENTATION WITH SKATE FISH CARTILAGE HYDROLYSATE ON KNEE JOINT FUNCTIONALITY AND DISCOMFORT IN ADULT POPULATION

Purpose: The tested product is a dried skate fish cartilage hydrolysate (SFCH) including collagen peptides together with glycosaminoglycans such as chondroitin sulfate and glucosamine sulfate . In a recent preclinical efficacy study, SFCH has shown a beneficial effect on pain and joint function in ACLT/pMMx osteoarthritis rat model (Henrotin et al., 2021). The aim of this study was to determine if 3 months of oral administration of SFCH can contribute to improve knee functionality and discomfort in an adult population with knee pain or mobility issues.

FORMULATION DEVELOPMENT OF ORLISTAT NANOCRYSTALS: IN VITRO CHARACTERIZATION AND IN VIVO STUDIES

Poor solubility of orlistat limits its luminal concentration and hence needs to be administered in higher doses, leading to drug related side effects. The aim of the present research was to investigate nanocrystallization approach to increase the solubility of orlistat using melt extrusion and high-pressure homogenization (HPH) methods. The effect of factors like type and amount of polymer, homogenization pressure and time, and number of cycles on orlistat solubility was investigated. A ~10-fold increase in the solubility of orlistat was attained using OPo11N with a subsequent increase in the dissolution rate of the drug. Poloxamer 188-orlistat nanocrystals (OPo11N) as compared to pure orlistat led to a decrease in T90%(20 mins for OPo11N and 51 mins for marketed sample). In vivo studies in female Sprague Dawley (SD) rats showed that post one month of oral administration the total cholesterol and low-density lipoproteins of female SD rats remained unchanged compared to the control group. The triglycerides content and high-density lipoproteins levels were significantly increased with increase in the treatment time i.e. 12 weeks compared to the group treated with pure orlistat drug. In conclusion, the NC approach could serve as an effective formulation strategy for solubility enhancement of orlistat.

Anorectic interaction and safety of 5-hydroxytryptophan/carbidopa plus phentermine or diethylpropion in rat.

Drug combinations are being studied as potential therapies to increase the efficacy or improve the safety profile of weight loss medications. This study was designed to determine the anorectic interaction and safety profile of 5-hydroxytryptophan (5-HTP)/carbidopa + diethylpropion and 5-HTP/carbidopa + phentermine combinations in rats. The anorectic effect of individual drugs or in combination was evaluated by the sweetened milk test. Isobologram and interaction index were employed to determine the anorectic interaction between 5-HTP/carbidopa and diethylpropion or phentermine. Plasma serotonin (5-HT) was measured by ELISA. Safety of repeated doses of both combinations in rats was evaluated using the tail sphygmomanometer, cardiac ultrasound, hematic biometry and blood chemistry. A single oral 5-HTP, diethylpropion or phentermine dose increased the anorectic effect, in a dose-dependent fashion, in 12 h-fasted rats. A dose of carbidopa at 30 mg/kg reduced the 5-HTP-induced plasmatic serotonin concentration and augmented the 5-HTP-induced anorectic effect. Isobologram and interaction index indicated a potentiation interaction between 5-HTP/30 mg/kg carbidopa + diethylpropion and 5-HTP/30 mg/kg carbidopa + phentermine. Chronic administration of experimental ED40 of 5-HTP/30 mg/kg carbidopa + phentermine, but not 5-HTP/30 mg/kg carbidopa + diethylpropion, increased the mitral valve leaflets area. Moreover, there were no other significant changes in cardiovascular, hematic or blood parameters. Both combinations induced around 20% body weight loss after 3 months of oral administration. Results suggest that 5-HTP/30 mg/kg carbidopa potentiates the anorectic effect of diethylpropion and phentermine with an acceptable safety profile, but further clinical studies are necessary to establish their therapeutic potential in the obesity treatment.

MINERALOGICAL COMPOSITION, STRUCTURE AND LITHOLYSIS OF URATE URINARY STONES FOR PATIENTS OF IVANOVO REGION

The quantitative mineralogical and chemical composition of urate urinary stones has been investigated using the X-ray powder method, scanning electron microscopy and X-ray spectral microanalysis for twenty five patients with urolithiasis of the Ivanovo region. The texture and surface composition of calculi have been carefully investigated and the peroral litholysis was simulated under laboratory conditions with dilute aqueous solutions of various pH values. The local change in the surface chemical composition for four stones during their destruction has been also studied via the X-ray spectral microanalysis. The main minerals of urate calculi are pure uric acid and insignificantly uric acid hydrates. No calculi composed of uric acid salts are observed. The main chemical elements of their surface are carbon, nitrogen and oxygen. The interaction of urate stones with litholytic solutions leads to a gradual decrease in their size, the effect being much more pronounced for smaller calculi. The results of X-ray spectral microanalysis show that the surface composition of stones composed of pure uric acid is almost constant during the treatment. Our results clearly indicate that oral litholysis of urate stones with appropriate citrate mixtures should be approached differentially depending on the composition of the calculus. In particular, for urate stones containing an appreciable amount of calcium oxalate hydrates, vitlocite or uric acid salts, litholytic therapy should be mainly applied as an additional technique to the extracorporeal shock wave or contact lithotripsy. For larger uric acid calculi, in turn, the effect of litholytic citrate monotherapy may be observed not earlier than after two or three months of oral administration of citrate mixtures.

Evaluation of Sex Hormone Levels in Benign Prostatic Hyperplasia Patients Treated with 5 Alpha-Reductase Inhibitor (Finasteride) in Amara city/Iraq

The present study aimed to determine the serum sex hormone levels among Benign Prostatic Hyperplasia (BPH) patients before and after 3 months of oral administration of 5-α reductase inhibitor(finasteride). Forty BPH patients and 40 healthy men from Amara city were involved in this study, their ages were between 40-59 year. They were all subjected to direct estimation of hormones by MinVidas method including Testosterone (T), Estradiol (E2), Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), Prolactin (PRL), and Dihydrotestosterone (DHT) before and after 3 months of treatment with 5α-reductase inhibitor (finasteride) (the healthy individuals didn’t take finasteride).The results showed that T level was significantly lower (P<0.05) in pre-treated compared to the post-treated patients and control group, whereas no significant difference was observed between the two latter groups. Levels of E2 - and DHT were significantly lower (P<0.01) in post-treated compared to the pre-treated patients with no significant difference with control group, while they were significantly higher (P<0.01) in pre-treated patients compared to control group. FSH and LH levels showed no significant differences in the pre-treated in comparison with post-treated and control groups. PRL levels insignificantly higher in pre-treated in comparison with post-treated patients, while significantly higher (P<0.05) in comparison with control group, with the later showing a significant lower (P<0.05) in comparison with post-treated patients. It is concluded that 5α-reductase inhibitor (finasteride) plays a role in decreasing levels of DHT and E2 which have vital roles in enlargement of prostate.

Beneficial Effects of Total Phenylethanoid Glycoside Fraction Isolated from Cistanche deserticola on Bone Microstructure in Ovariectomized Rats

The present study was designed to estimate the antiosteoporotic activity of total phenylethanoid glycoside fraction isolated from C. deserticola (CDP) on rats induced by ovariectomy (OVX) as well as the related mechanisms. After 3 months of oral administration, the decreased bone mineral density, serum Ca, and P in OVX rats were recovered and the deteriorated trabecular bone microarchitecture was partly improved by CDP (60, 120, and 240 mg/kg) intervention, the activities of bone resorption markers were downregulated, and the bioactive of the bone formation index was upregulated; meanwhile, the content of MDA was declined, and GSH was increased by CDP treatment. Compositionally, 8 phenylethanoid glycoside compounds were identified in CDP, with the total contents quantified as 50.3% by using the HPLC method. Mechanistically, CDP declined the levels of TRAF6, RANKL, and RANK, thus suppressing RANKL/RANK/TRAF6-induced activation of downstream NF-κB and PI3K/AKT signaling pathways and ultimately preventing activities of the key osteoclastogenic proteins of NFAT2 and c-Fos. All of the above data implied that CDP exhibited beneficial effects on bone microstructure in ovariectomized rats, and these effects may be related to the NF-κB and PI3K/AKT signaling pathways which were triggered by the binding of RANKL, RANK, and TRAF6.

Hepatoprotective and nephroprotective effects of Trigonella foenum-graecum L. (Fenugreek) seed extract against sodium nitrite toxicity in rats

Introduction: Feeding habits and environmental factors may rival genetic susceptibility as etiological factors related to various cancers. Humans are continuously exposed to many synthetic food additives, one of which is sodium nitrite (NaNO2). There is a direct correlation between increases in consumption of nitrite-treated products and incidence of tissue damage, hepatotoxicity, nephrotoxicity and some types of cancer. The objective of this study was to investigate the protective effects of Trigonella foenum-graecum (TFG) on NaNO2-induced hepatotoxicity and nephrotoxicity.
 Methods: Forty rats were randomly assigned (10 per group) to control (physiological saline solution), TFG (150 mg/kg/day), NaNO2 (80 mg/kg/day), and NaNO2+TFG (80 mg/kg/day + 150 mg/kg/day) groups. This group was offered TFG seed extract two hours before NaNO2. At the end of three months, the rats were decapitated, and blood, kidney and liver tissues were removed.
 Results: Three months of oral administration of NaNO2 increased serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, creatinine, and pro-inflammatory cytokine levels in the liver and kidney tissues [except for liver Interleukin 1 alpha (IL-1a)] of rats. Serum AST, ALT, urea, creatinine, liver IL-6, and kidney tumor necrosis factor-a (TNF-a), IL-6, IL-1a levels significantly decreased in the NaNO2+TFG group compared to the NaNO2 group. Pathological examinations, it was determined show that exogenously administered TFG could alleviate the effects of NaNO2 hepatotoxicity and nephrotoxicity.
 Conclusions: Our results suggest that exogenous TFG mitigates NaNO2-administration induced hepatotoxicity and nephrotoxicity. TFG extract exerted antioxidative and anti-inflammatory effects, and played a significant role in preventing hepatic and renal damage induced by chronic NaNO2 administration.

Management of Stroke through Virechana: A Case Report

Stroke is a leading cause of adult neurological disability and represents an enormous health problem worldwide. It describes a clinical syndrome, which can be caused by a number of different pathologies, rather than a single disease. In Ayurveda, Pakshaghata can be compared to hemiplegia which is the presentation of stroke. In this study a case report of stroke is being presented. The patient was treated on the lines of Ayurvedic management involving Virechana as the chief treatment modality. On completion of Virechana karma, the case was subjected to one month of oral administration of Masha baladi kwatha, along with Sarvanga abhyanga and Vashpa swedana. The observations made after the treatment through assessment on various subjective and objective parameters were convincing and led to scope of further adjunction of other Panchakarma therapies after Virechana as the baseline therapy.

Enhanced solubility, oral bioavailability and anti-osteoporotic effects of raloxifene HCl in ovariectomized rats by Igepal CO-890 nanomicelles

The purpose of the present study was to enhance the bioavailability and anti-osteoporotic effects of raloxifene HCl (RH) by increasing its solubility and inhibition of the p-glycoprotein pump using surfactant micelles of Igepal CO-890. The micelles were prepared by the direct method and their critical micellar concentration, drug dissolution rate, saturated solubility, drug loading and surface morphology were defined. The cytotoxicity of Igepal CO-890 and its ability to inhibit the p-glycoprotein pump were studied on Caco-2 cells. The pharmacokinetic parameters were analyzed by oral administration of a single dose of 15 mg/kg in Wistar rats. Anti-osteoporotic effects were studied by measuring the calcium, phosphorous, and uterus weight of rats after one month of oral administration of 6 mg/kg/day of RH in ovariectomized rats. Igepal CO-890 micelles enhanced the RH solubility by about two-fold. The FT-IR and DSC studies indicated no interaction between the drug and the surfactant. XRD spectrum showed an amorphous state of RH in the micelles. The p-glycoprotein pump was inhibited by Igepal CO-890 in Caco-2 cells comparable to verapamil. Micelles increased the uterine weight and decreased the serum calcium and phosphorus significantly compared to the untreated drug. Oral bioavailability of RH increased about four-fold by nanomicelles.

Cyanamide-Induced Hepatotoxicity and the Potential Protective Role of Pomegranate Seed Extract in Adult Male Albino Rats

Background: Dormex, which is used as agricultural fertilizer, contains cyanamide as an active ingredient. Pomegranate fruits enclose numerous polyphenols that guard normal cells against oxidative stress. Aim of the work: to study the hepatotoxic effects of Dormex and assess the protective capacity of pomegranate seed extract (PSE) in rats after 3 months of oral administration. Material & methods: Sixty mature male albino rats were distributed to; Group I, II: rats were given 0.1 ml distilled water/kg/day and 400 mg/kg/day of pomegranate seed extract (PSE), respectively. Group III: divided into two subgroups in which rats received 30 & 60 mg/kg/day Dormex, respectively. Group IV: divided into two subgroups in which rats were given the same dose of Dormex plus PSE. Body and liver weights, serum albumin, total bilirubin and liver enzymes were assessed. Hepatic malondialdehyde (MDA), glutathione reductase and catalase activities were evaluated. Liver specimens were studied with H. &E., Mallory's trichrome and caspase-3 immunostaining. Results: The hepatic index, liver enzymes, bilirubin, and MDA were significantly increased (P˂0.001), while albumin, glutathione reductase, and catalase were lowered significantly in rats of experimental groups compared to the control (P˂0.001). All these assessed parameters were within normal range in the protected groups. The histopathological changes included liver inflammation, degeneration and fibrosis, in addition to apoptosis. Treatment with PSE markedly prevented the occurrence of these abnormalities. Conclusion: Cyanamide prompts oxidative stress that compromises the liver function and eventually liver fibrosis results. These toxic effects are dose related. The PSE exhibits hepatoprotective effects and highlights the possibility of its use as a protective agent in individuals at high risk of Dormex toxicity.

A Novel ACE Inhibitory Peptide Ala-His-Leu-Leu Lowering Blood Pressure in Spontaneously Hypertensive Rats.

Ala-His-Leu-Leu (AHLL) was isolated and purified from the loach (Misgurnus anguillicaudatus) hydrolysate in our previous study. The aim of this study was to investigate the antihypertensive effects of angiotensin-I-converting enzyme (ACE) inhibitory peptide AHLL in spontaneously hypertensive rats (SHRs). AHLL showed good antihypertensive effects in SHRs during the long-term oral administration and no allergic reactions or coughing were observed. After 2 months of oral administration of AHLL, the body weight growth was normal. The decrements in systolic blood pressure of the high dose (5 mg/kg bw) and the low dose of AHLL (1 mg/kg bw) treatment groups were 22.1 and 5.0 mmHg at week 8, respectively. Compared to the control group, the concentrations of triglyceride and sodium in serum were reduced significantly in the high-dose group after 2 months. The ACE activity of kidney and lung decreased significantly, which indicated that AHLL exerted an antihypertensive effect on kidney and lung and they were the target sites of AHLL. These results strongly supported the in vivo antihypertensive mechanism of AHLL.

Efficacy of oral administration of yoghurt supplemented with a preparation containing hyaluronic acid (Mobilee™) in adults with mild joint discomfort: a randomized, double-blind, placebo-controlled intervention study

A prospective, randomized, double-blind, placebo-controlled study was designed with 40 healthy individuals with joint discomfort. The effect of oral supplementation with a natural product containing hyaluronic acid included in a yoghurt matrix was evaluated in terms of functional and quality-of-life parameters. An isokinetic dynamometer was used to measure maximum muscle strength, total work and mean power. Participants were divided into 2 groups (n = 20) and ate yoghurt that was either supplemented or not supplemented with the hyaluronic acid product daily for a period of 90 days. The increase in the maximum peak torque of the knee extensors compared to baseline values was 7.6 ± 7.6 Nm for the supplemented yoghurt group and 2.5 ± 4.7 Nm for the control group at 180°/s (P = 0.0582), and 6.5 ± 5.8 Nm for the supplemented yoghurt group and −1.0 ± 7.1 Nm for the control group at 240°/s (P < 0.05). The same pattern of response was observed in total work and in mean power (P < 0.05). Differences were less pronounced in the knee flexors. No differences were detected in the Lequesne score and SF-36 survey except for the social functioning subscale at 1 month follow-up. This prospective placebo-controlled nutritional study confirmed that 3 months of oral administration of a natural product containing HA (Mobilee™) in healthy individuals with joint discomfort of the knee provides improvements in muscle strength.

Effect of the anti-diabetic drug metformin on bone mass in ovariectomized rats

Recent studies have reported bone loss in the patients with diabetes and a direct osteogenic effect of metformin on osteoblast-like cells in culture. In this study, we investigated the action of metformin on bone mass in ovariectomized (OVX) rats. Three months after either a sham surgery or bilateral ovariectomy, thirty-two female Sprague–Dawley rats were randomly assigned into four groups: (1) Sham group; (2) OVX group; (3) OVX + metformin (50 mg/kg/day) group; and (4) OVX + metformin (100 mg/kg/day) group. After 2 months of oral administration with or without metformin, tibiae were harvested for dual energy X-ray absorptiometry, micro-computed tomography (micro-CT) and histology analysis, while the bone marrow cells from tibiae were collected for measurement of the mRNAs expressions for three osteoblast genes and estrogen receptors alpha by the use of real-time RT-PCR. We found that the impaired bone density and quality induced by bilateral ovariectomy were significantly improved by the treatment of metformin (both 50 and 100 mg/kg/day), and this action could be partly mediated by regulating bone marrow cells development through induction of mechanisms regulating osteoblast markers core binding factor a1 and LDL receptor-related protein 5. These findings provide new evidence that the anti-diabetic drug metformin has a direct inhibition effect on bone loss in OVX rats, in addition to its well-documented osteogenic potency in vitro.

Studies on the glycemic and lipidemic effect of Murraya koenigii in experimental animals

Diabetes is often accompanied by lipid abnormalities, which contribute significantly to cardiovascular morbidity and mortality in diabetic patients. Previously, we have demonstrated potent hypoglycemic activity of lyophilized aqueous extract of Murraya koenigii leaves in normal and alloxan induced diabetic rabbits for short duration of 6 h. In this study, we examined the effect of 1 month oral administration of Murraya koenigii aqueous leaves extract in normal and STZ induced severe diabetic rats, at the dose of 300 mg/kg bw, on various biochemical parameters, viz., fasting blood glucose (FBG), total cholesterol (TC), HDL-cholesterol (HDL), triglyceride (TG), alkaline phosphatase (ALKP), serum glutamate oxaloacetate and pyruvate transaminases (SGOT and SGPT) and serum creatinine. In case of diabetic animals fasting blood glucose (FBG) levels of treated animals reduced by 48.2% after 30 days treatment with the aqueous leaves extract. A fall of 19.2 and 30.8% in TC and 22.97 and 37.1% in TG levels were also observed in the case of treated normal as well as diabetic rats, respectively. Feeding the extract increased the HDL-cholesterol level by 16 and 29.4% in normal and diabetic rats, respectively, as compared with their initial values. In the normal rats after 1 month of oral administration of the extract SGOT and SGPT levels were decreased by 21.7 and 25.0%. Serum alkaline phosphatase values of the treated normal animals were also reduced by 33% while negligible change was observed in the normal control animals. In the case of diabetic rats, SGOT and SGPT levels were reduced by 36.7 and 32.2%, respectively, whereas ALKP levels decreased by 39.7% after 1 month oral administration of the extract. The serum creatinine levels decrease in normal as well as in the diabetic animals by 17.75 and 18.2%, respectively, as compared to initial values. In the diabetic control animals the urinary sugar remains at +4 level but there was a decrease of 75% in urine sugar in the case of treated diabetic rats. This indicates that the aqueous extract of Murraya koenigii has favorable effect in bringing down the severity of diabetes.

S4-04-06: Thiadiazolidindiones, selective glycogen synthase kinase-3 inhibitors as potential therapeutic agents for Alzheimer’s disease and other tauopathies

GSK–3 is a serine/threonine kinase with an astoundingly diverse number of actions in intracellular signalling systems. It plays crucial roles in several human diseases having great potential for therapeutic intervention. Currently, GSK–3 inhibitors arise as promising drugs for the pharmacotherapy of several acute pathologies as cancer, diabetes, stroke, mood disorders, inflammation or Alzheimer′s disease (AD), among others. Recently, a large body of evidence has accumulated linking GSK–3 with tau hyperphosphorylation, and more recently, Aβ production, the two pathological hallmarks of AD. The small heterocyclic thiadiazolidindiones (TDZDs) represent the first non–ATP competitive GSK3 inhibitors reported to date and have been proposed as new disease–modifying agents for the effective treatment of neurodegenerative disorders where tau phosphorylation plays a key role, such as AD. TDZDs have favourable ADME–Tox drugable properties and their therapeutic potential has been proved using different animal models. A prolonged oral administration of a TDZD compound to the GSK3β conditional transgenic mice (Tet/GSK3β) produces a significant decrease on tau phosphorylation both in the hippocampus and cortex areas where the transgene is expressed. Moreover, this TDZD compound is able to improve cognition (by object recognition test), and diminish the cortex and hippocampus amyloid plaque load in an APP–PS1 double transgenic mouse after 2 months of oral administration. The positive observed effects in these studies together with some other neuroprotective properties found on this family of compounds, confirm the potential of TDZDs as new therapeutic agents for the inhibition of GSK3 and tau phosphorylation in AD and other tauopathies.

Improved haemorrheological properties by Ginkgo biloba extract (Egb 761) in type 2 diabetes mellitus complicated with retinopathy

Background & Aims: Abnormal haemorrheological property changes in erythrocyte deformability, plasma and blood viscosity, and blood viscoelasticity may play very important roles in the development of microangiopathies in diabetes mellitus (DM). In this study, we demonstrate the improvement in abnormal haemorrheological parameters in DM with ingestion of Ginkgo biloba extract 761 (Egb 761). Methods: Haemorrheological parameters before and 3 months after Egb 761 oral ingestion were determined in 25 type 2 DM patients with retinopathy. These parameters included lipid peroxidation stress of erythrocytes, erythrocyte deformability, plasma and blood viscosity, blood viscoelasticity, and retinal capillary blood flow velocity. Results: After taking Egb 761 orally for 3 months, the blood viscosity was significantly reduced at different shear rates, by 0.44±0.10 ( γ=400), 0.52±0.09 ( γ=150) and 2.88±0.57 ( γ=5). Viscoelasticity was significantly reduced in diabetic patients by 3.08±0.78 (0.1 Hz). The level of erythrocyte malondialdehyde (MDA) was reduced by 30%; however, the deformability of erythrocyte was increased by 20%. And lastly, retinal capillary blood flow rate was increased from 3.23±0.12 to 3.67±0.24 cm min −1. Conclusion: In this preliminary clinical study, 3 months of oral administration of Egb 761 significantly reduced MDA levels of erythrocytes membranes, decreased fibrinogen levels, promoted erythrocytes deformability, and improved blood viscosity and viscoelasticity, which may facilitate blood perfusion. Furthermore, it effectively improved retinal capillary blood flow rate in type 2 diabetic patients with retinopathy.