Frequency: Quarterly E- ISSN: 0976-7509 P- ISSN: 2229-4171 IBI Factor: 4.1 Abstracted/ Indexed in: Ulrich's International Periodical Directory, Google Scholar, SCIRUS, Genamics Journal Seek, PSOAR, getCITED, JOURNAL directory, InfoBase Index, EBSCO Information Services
Quarterly published in print and online "Inventi Impact: Molecular Pharmacology" publishes high quality unpublished as well as high impact pre-published research and reviews catering to the needs of researchers and professionals. The journal covers all the areas in the growing field of molecular pharmacology. It aims to cover the developments in cellular and molecular pharmacology with a major emphasis on the mechanism of action of drugs under development, innovative pharmacological technologies, cell signaling, transduction pathway analysis, genomics, and proteomics.
Background: Increased functionality of efflux transporters at the blood-brain barrier may contribute to decreased\r\ndrug concentrations at the target site in CNS diseases like epilepsy. In the rat, pharmacoresistant epilepsy can be\r\nmimicked by inducing status epilepticus by intraperitoneal injection of kainate, which leads to development of\r\nspontaneous seizures after 3 weeks to 3 months. The aim of this study was to investigate potential changes in Pglycoprotein\r\n(P-gp) expression and functionality at an early stage after induction of status epilepticus by kainate.\r\nMethods: (R)-[11C]verapamil, which is currently the most frequently used positron emission tomography (PET)\r\nligand for determining P-gp functionality at the blood-brain barrier, was used in kainate and saline (control) treated\r\nrats, at 7 days after treatment. To investigate the effect of P-gp on (R)-[11C]verapamil brain distribution, both groups\r\nwere studied without or with co-administration of the P-gp inhibitor tariquidar. P-gp expression was determined\r\nusing immunohistochemistry in post mortem brains. (R)-[11C]verapamil kinetics were analyzed with approaches\r\ncommon in PET research (Logan analysis, and compartmental modelling of individual profiles) as well as by\r\npopulation mixed effects modelling (NONMEM).\r\nResults: All data analysis approaches indicated only modest differences in brain distribution of (R)-[11C]verapamil\r\nbetween saline and kainate treated rats, while tariquidar treatment in both groups resulted in a more than 10-fold\r\nincrease. NONMEM provided most precise parameter estimates. P-gp expression was found to be similar for kainate\r\nand saline treated rats.\r\nConclusions: P-gp expression and functionality does not seem to change at early stage after induction of\r\nanticipated pharmacoresistant epilepsy by kainate....
Panax notoginseng (PN) has been used as a qi- and blood-activating (Huoxue) drug for thousands of years in China. It has also\nbeen widely used as an anticancer drug at present. As a Huoxue drug, the effect of PN on hematopoietic differentiation in tumorbearing\nbody has been paid more and more attention. Our research found that panax notoginseng saponins (PNS), especially\npanaxadiol saponins (PDS) and its aglucon 20(S)-Protopanaxdiol (PPD), could improve the immunosuppressive state by regulating\nthe abnormal hematopoietic differentiation in a tumor-bearing body by multiple ways����.....
: Various regulatory and structural proteins in myocardium found to be responsive to thyroid hormone. However, use of thyroid hormone is limited by cardiac effects. This study was undertaken to explore the cardioprotective action along with general toxicological impact induced by the 3, 5, 3’-triiodothyronine (T3) in a surgically developed hypothyroid female Wistar rats by administration of T3 at the dose of 2, 10, 20 & 40 µg/kg orally for 7 days. Increased alertness and locomotor activity was observed from 10µg/kg. Normalization of heart rate and body temperature was noticed at 10 and 20µg/kg dose of T3 treated hypothyroid rats when compared with normal rats. Low density lipoprotein, triglyceride, total protein and creatinine levels were altered in T3 treated rats marked at 40µg/kg. Dose dependent higher heart weight was observed, with significant from 20µg/kg in comparisons with hypothyroid rat, however rat treated with 2 and 10µg/kg shown normal weight and is comparable with euthyroid rats. Myosin heavy chain alpha and beta gene expression ratio tend toward normalization at 10 and 20µg/kg and was comparable with normal rats. Histopathological examination of heart revealed mononuclear cells infiltration with of fibroblast proliferation at 10 and 20µg/kg. Based on the finding of restoration of cardiac function in terms of heart rate, heart weight, body temperature, myosin gene expression alpha and beta ratio and proliferation of fibroblast in heart tissue indicate T3 may be explored further in treatment of hypothyroidism by precise dose selection for cardiac protective function....
The objective of this research is to generate leads for developing our ultimate\npoly-active molecules with utility in central nervous system (CNS) diseases. Indeed, poly-active\nmolecules capable of mitigating brain free radical damage while enhancing acetylcholine signaling\n(via cholinesterase inhibition) are still being sought for combating Alzheimerââ?¬â?¢s disease (AD).\nWe differentiate ââ?¬Å?poly-activeââ?¬Â agents from ââ?¬Å?multi-targetââ?¬Â ones by defining them as single\nmolecular entities designed to target only specific contributory synergistic pharmacologies in\na disease. For instance, in AD, free radicals either initiate or act in synergy with other\npharmacologies, leading to disease worsening. For this preliminary report, a total of 14\n(i.e., 4,5-dimethoxy-2-nitrobenzohydrazide plus 1-(1-benzylpiperidin-4-yl)ethan-1-one) derivatives\nwere synthesized and screened, in silico and in vitro, for their ability to scavenge free radicals and\ninhibit acetylcholinesterase (AChE)/butyrylcholinesterase (BuChE) enzymes. Overall, six derivatives\n(4a, 4d, 4e, 4f, 4g, 9b) exhibited potent (>30%) antioxidant properties in the oxygen radical absorbance\ncapacity (ORAC) assay. The antioxidant values were either comparable or more potent than the\ncomparator molecules (ascorbic acid, resveratrol, and trolox). Only three compounds (4d, 9a, 9c)\nyielded modest AChE/BuChE inhibitions (>10%). Please note that a SciFinder substance data base\nsearch confirmed that most of the compounds reported herein are new, except 9a and 9c which are\nalso commercially available....
Instability of repetitive sequences originates from strand misalignment during repair or replicative DNA synthesis. To investigate the activity of reconstituted T4 replisomes across trinucleotide repeats (TNRs) during leading strand DNA synthesis, we developed a method to build replication miniforks containing a TNR unit of defined sequence and length. Each minifork consists of three strands, primer, leading strand template, and lagging strand template with a 5' single-stranded (ss) tail. Each strand is prepared independently, and the minifork is assembled by hybridization of the three strands. Using these miniforks and a minimal reconstituted T4 replisome, we show that during leading strand DNA synthesis, the dNTP concentration dictates which strand of the structure-forming 5'CAG/5'CTG repeat creates the strongest impediment to the minimal replication complex. We discuss this result in the light of the known fluctuation of dNTP concentration during the cell cycle and cell growth and the known concentration balance among individual dNTPs....
Background: Mitochondrial dysfunction is associated with obesity and various obesity-associated pathological\nconditions including glucose intolerance. 5-Aminolevulinic acid (ALA), a precursor of heme metabolites, is a natural\namino acid synthesized in the mitochondria, and various types of cytochromes containing heme contribute to aerobic\nenergy metabolism. Thus, ALA might have beneficial effects on the reduction of adiposity and improvement of glucose\ntolerance through its promotion of heme synthesis. In the present study, we investigated the effects of ALA combined\nwith sodium ferrous citrate (SFC) on obesity and glucose intolerance in diet-induced obese mice.\nMethods: We used 20-weeks-old male C57BL/6J diet-induced obesity (DIO) mice that had been fed high-fat diet from\n4th week or wild-type C57BL/6J mice. The DIO mice were orally administered ALA combined with SFC (ALA/SFC) for\n6 weeks. At the 4th and 5th week during ALA/SFC administration, mice were fasted for 5 h and overnight, respectively\nand used for oral glucose tolerance test. After the ALA/SFC administration, the plasma glucose levels, weight of white\nadipose tissue, and expression levels of mitochondrial oxidative phosphorylation (OXPHOS) complexes were examined.\nFurthermore, the effects of ALA/SFC on lipid content and glucose uptake were examined in vitro.\nResults: Oral administration of ALA/SFC for 6 weeks reduced the body weight by about 10% and the weight of white\nadipose tissues in these animals. In vitro, ALA/SFC reduced lipid content in mouse 3T3-L1 adipocytes in a\ndose dependent manner, and enhanced glucose uptake in 3T3-L1 adipocytes by 70ââ?¬â??90% and rat L6 myoblasts by 30% at\n6 h. Additionally, oral administration of ALA/SFC reduced plasma glucose levels and improved glucose tolerance in DIO\nmice. Furthermore, ALA/SFC enhanced the expression of OXPHOS complexes III, IV, and V by 40ââ?¬â??70% in white adipose\ntissues of DIO mice, improving mitochondrial function.\nConclusions: Our findings indicate that ALA/SFC is effective in the reduction of adiposity and improvement of glucose\ntolerance, and that the induction of mitochondrial OXPHOS complex III, IV, and V by ALA/SFC might be an essential\ncomponent of the molecular mechanisms underlying these effects. ALA/SFC might be a useful supplement for obesity\nand obesity-related metabolic disease such as type 2 diabetes mellitus....
Cell surface receptors have been shown to be the sites of disease infectivity in living organisms in two previous studies. The cell surface receptors were shown to have two reactive heads or terminals with one head being half the size and shape of the other head. A new study reported here involved a comparism of the effects of acid and alkaline herbal extracts on Candida albicans infected cell surface receptors at human cutaneous Candida infection sites. The effects of three acid herbal extracts on cutaneous Candida albicans infection were compared with those of three alkaline herbal extracts. The three alkaline herbal extracts were the extract of Azadirachta indica leaves; the extract of Vernonia amygdalina leaves and the pulp of ripe Carica papaya (pawpaw) fruit. The three acid herbal extracts were the extract of Aniseed (ugugo) [a tiny Central African moderately hot spice] seeds; the juice of Gambeya albida (family sapotaceae) fruit (a local Nigerian fruit that has a high content of ascorbic acid); and the extract of curry leaves.The mode of data collection was the observation and photographing of the effects of the acid and alkaline herbal extracts on cutaneous Candida albicans infection sites. The results of the study showed that candida albicans tissues infected the human skin by attaching themselves to cell surface receptors of skin epithelial cells.They also showed that the cell surface receptor on the human skin to which the ‘root’ (centromere) of a candida colony attached itself had two receptive ends, to which an infective organism attached itself (and to which an anti-infective agent also attached to eliminate the infective agent). These two ends consisted of an excitatory or ‘muscarinic’ end which was stimulated by the acidic herbal extracts and an inhibitory or ‘adrenergic’ end to which the alkaline herbal extract molecules attached themselves to produce inhibitory effects on the stimulatory effects of the attached candida tissues. The excitatory (stimulatory) harsh stinging actions of the acid heral extracts were interpreted as contractile or muscarinic-like action. The cell surface receptor head to which the acid herbal extracts attached to exercise the muscarinic action to eliminate attached Candida tissues was termed a muscarinic receptor site. From the structure of muscarine (that contains 2 indole ring structures), the muscarinic receptor site was infered to be to be an indole ring structure and the inhibitory or ‘adrenergic ‘end to be a benzene ring structure. Since the two heads of the cell surface receptor lie side by side, a placement of an indole ring to the right of a benzene ring produced the 5-hydroxytryptamine nucleus structure. Conclusions: The study therefore concludes that the cell surface receptor to which the roots of candida albicans attached themselves in the human skin is the 5- hydroxytryptamine receptor. This means that under the normal body functioning situation, 5-hydroxytryptamine was the endogenous body substance that guarded cell surface receptors against the attachment and habitation of the Candida albicans infective organisms. The findings of this study have therefore established 5-hydroxytrptamine (5-HT or Serotonin) as the endogenous mediator of the human body’s defence and cell surface receptors to which candida albicans (and by implication , all infective organisms and antigens / toxins) attached themselves to infect and damage the body) as the receptors of 5-hydroxytryptamine. Since body defence is a part of normal physiological body functioning (as the mediator of the body’s defence also ensures that the body is working normally at all times), 5-hydroxytryptamine is therefore through the findings of this study also the endogenous mediator of all normal human body (physiological) functioning. This means that 5-hydroxytryptamine (5-HT or Serotonin) mediates all activities of normal human body functioning. The conclusions of this study about 5-HT as the endogenous mediator of...
Abstract: \r\nIntroduction: Cell surface receptors have been shown to be the sites of disease infectivity in living organisms in two previous studies. The cell surface receptors were shown to have two reactive heads or terminals with one head being half the size and shape of the other head. \r\nProblem Statement: A new study reported here involved a comparism of the effects of acid and alkaline herbal extracts on Candida albicans infected cell surface receptors at human cutaneous Candida infection sites. \r\nApproach: The effects of three acid herbal extracts on cutaneous Candida albicans infection were compared with those of three alkaline herbal extracts. The three alkaline herbal extracts were the extract of Azadirachta indica leaves; the extract of Vernonia amygdalina leaves and the pulp of ripe Carica papaya (pawpaw) fruit. The three acid herbal extracts were the extract of Aniseed (ugugo) [a tiny Central African moderately hot spice] seeds; the juice of Gambeya albida (family sapotaceae) fruit (a local Nigerian fruit that has a high content of ascorbic acid); and the extract of curry leaves.\r\nThe mode of data collection was the observation and photographing of the effects of the acid and alkaline herbal extracts on cutaneous Candida albicans infection sites.\r\nResults: The results of the study showed that candida albicans tissues infected the human skin by attaching themselves to cell surface receptors of skin epithelial cells.They also showed that the cell surface receptor on the human skin to which the ââ?¬Ë?rootââ?¬â?¢ (centromere) of a candida colony attached itself had two receptive ends, to which an infective organism attached itself (and to which an anti-infective agent also attached to eliminate the infective agent). These two ends consisted of an excitatory or ââ?¬Ë?muscarinicââ?¬â?¢ end which was stimulated by the acidic herbal extracts and an inhibitory or ââ?¬Ë?adrenergicââ?¬â?¢ end to which the alkaline herbal extract molecules attached themselves to produce inhibitory effects on the stimulatory effects of the attached candida tissues.\r\nThe excitatory (stimulatory) harsh stinging actions of the acid heral extracts were interpreted as contractile or muscarinic-like action. The cell surface receptor head to which the acid herbal extracts attached to exercise the muscarinic action to eliminate attached Candida tissues was termed a muscarinic receptor site. From the structure of muscarine (that contains 2 indole ring structures), the muscarinic receptor site was infered to be to be an indole ring structure and the inhibitory or ââ?¬Ë?adrenergic ââ?¬Ë?end to be a benzene ring structure.\r\n Since the two heads of the cell surface receptor lie side by side, a placement of an indole ring to the right of a benzene ring produced the 5-hydroxytryptamine nucleus structure.\r\nConclusions: The study therefore concludes that the cell surface receptor to which the roots of candida albicans attached themselves in the human skin is the 5- hydroxytryptamine receptor. This means that under the normal body functioning situation, 5-hydroxytryptamine was the endogenous body substance that guarded cell surface receptors against the attachment and habitation of the Candida albicans infective organisms.\r\nThe findings of this study have therefore established 5-hydroxytrptamine (5-HT or Serotonin) as the endogenous mediator of the human bodyââ?¬â?¢s defence and cell surface receptors to which candida albicans (and by implication , all infective organisms and antigens / toxins) attached themselves to infect and damage the body) as the receptors of 5-hydroxytryptamine.\r\nSince body defence is a part of normal physiological body functioning (as the mediator of the bodyââ?¬â?¢s defence also ensures that the body is working normally at all times), 5-hydroxytryptamine is therefore through the findings of this study also the endogenous mediator of all normal human body (physiological) functioning. This means that 5-hydroxytryptamine (5-HT or Serotonin) mediates all activities of normal human body functi...
Cirrhosis is characterized by the formation of regenerative nodules in liver parenchyma surrounded by fibrous septa\r\ndue to chronic liver injury. Cirrhosis occurs due to necrosis of liver cells followed by fibrosis and nodule formation. The liver\r\nstructure becomes abnormal and interferes with liver blood flow and function and leads to portal hypertension and impaired\r\nhepatocytes function. Chronic liver diseases represent a significant health problem across the globe with liver cirrhosis. The\r\nexact prevalence of cirrhosis worldwide is still unknown as the clinical spectrum ranges from indolent, asymptomatic to\r\ncomplete hepatic decompensation. Diagnosis of cirrhosis includes serological test, histological test, transient elastography and\r\nradio techniques like ultrasonography, computerised tomography scan and magnetic resonance imaging. Ursodeoxycholic acid\r\nis used for treatment of primary biliary cirrhosis. For treatment of autoimmune hepatitis prednisone and azathioprine are used.\r\nFor hepatitis B and C treatment interferon and antiviral agents are used. For treatment of hemochromatosis phlebotomy is used.\r\nFor treatment of wilson disease, trientine and zinc are used. Liver transplantation is main curative option for treatment of liver\r\ncirrhosis, but it possesses significant risk to the patient....
Technical advances in recent years have made the application of controlled low temperatures a feasible proposition in many branches of surgery. The benefits of cold have been appreciated for many thousands of years. In the last decade there has been a proliferation of reports on the uses of cryotherapy; nevertheless, many of the applications are still experimental, or await the test of time. Cryotherapy is the deliberate destruction of tissue by application of extreme cold. This review highlights on the various aspect like the different terms, techniques, principles and applications of cryotherapy. Cryotherapy now days getting popularity due to cure rate as well as the advancement in the equipments....
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