Probiotic characterization of Lactiplantibacillus plantarum HOM3204 and its restoration effect on antibiotic-induced dysbiosis in mice

The purpose of this study was to evaluate the probiotic characteristics of Lactiplantibacillus plantarum HOM3204 isolated from homemade pickled cabbage and to examine its restoration effect on antibiotic-induced dysbiosis in mice. Lact. plantarum HOM3204 tolerated simulated gastric and intestinal juices with a 99·38% survival rate. It also showed strong adhesion ability (3·45%) to Caco-2 cells and excellent antimicrobial activity against foodborne pathogens in vitro. For safety (antibiotic susceptibility) of this strain, it was susceptible to all the tested seven antibiotics. Lact. plantarum HOM3204 had good stability during storage, especially in cold and frozen conditions. Furthermore, Lact. plantarum HOM3204 significantly restored the gut microbiota composition by increasing the abundance of Lactobacilli and Bifidobacteria and decreasing Enterococci, and improved antioxidative function by raising the concentrations of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in serum of antibiotic-induced dysbiosis in mice. These results suggest that Lact. plantarum HOM3204 could be a potential probiotic as a functional food ingredient.     

Geography of underweight and overweight among women in India: A multilevel analysis of 3204 neighborhoods in 26 states

We investigated the geographic distribution and the relationship with neighborhood wealth of underweight and overweight in India. Using multilevel modeling techniques, we calculated state-specific smoothed shrunken state residuals of overweight and underweight, neighborhood and state variation of nutritional status, and the relationships between neighborhood wealth and nutritional status of 76,681 women living in 3204 neighborhoods in 26 Indian states. We found a substantial variation in overweight and underweight at the neighborhood and state levels, net of what could be attributed to individual-level factors. Neighborhood wealth was associated with increased levels of overweight and decreased levels of underweight, and was found to modify the relationship between personal living standard and nutritional status. These findings suggest that interventions to address the double burden of undernutrition and overnutrition in India must take into account state and neighborhood characteristics in order to be successful.     

The role of T-type calcium channels in morphine analgesia,development of antinociceptive tolerance and dependence to morphine,and morphine abstinence syndrome

Involvement of T-type voltage dependent Ca2+ channels (VDCCs) on morphine antinociception, in the development of tolerance and dependence to morphine, and naloxone-precipitated abstinence syndrome in morphine dependent mice was examined by using mibefradil, a T-type VDCCs blocker. Mice were rendered tolerant and dependent on morphine by subcutaneous (s.c.) implantation of a morphine pellet containing 75 mg of morphine base for 72 hr. The tail-flick test was used to assess the nociceptive threshold. Coadministration of acute mibefradil (10 mg/kg, i.p.) with morphine enhanced the antinociceptive effects of acute morphine. Repeated mibefradil administration (10 mg/kg, i.p., just before, 24 and 48 hr after morphine pellet implantation) completely blocked the development of tolerance to the antinociceptive effect of morphine and even by this effect reached supersensitivity to morphine. However, repeated mibefradil treatment did not alter the development of dependence to morphine assessed by the A(50) values of naloxone (s.c.) required to precipitate withdrawal jumping 72 hr after morphine pellet. But, acute mibefradil (10, 30, and 50 mg/kg, i.p.) dose dependently decreased the expression of morphine abstinence syndrome when given directly 30 min prior to naloxone (0,05 mg/kg, s.c.) 72 hr after morphine pellet. These results indicate a critical role of T-type VDCCs in morphine antinociception, the development of tolerance to the antinociceptive effects of morphine and in morphine abstinence syndrome.     

Immunomodulation by morphine and marijuana

The immunomodulatory effects of morphine and the active components of marijuana, particularly tetrahydrocannabinol, on various aspects of the host immune parameters include alterations in humoral, cell-mediated and innate immunity. Most studies have shown immunosuppressive effects due to use of these abused substances, although there are reports that they may not produce any deleterious effect and may even enhance some aspects of host immunity. They reduce resistance to cancer growth and microbial pathogens in animals.     

Interaction between morphine and lysine

The study by the molecular orbital theory displayed that morphine and lysine make two types of the interactions between them: type (A) by three hydrogen bondings and type (B) by one hydrogen bonding accompanied with a proton transfer. The stabilization energies were 45.3 and 34.9 kcal/mol for type (A) and type (B), respectively. The characters of these interactions are striking compared to the interactions of morphine with the other amino acids, suggesting that lysine is the binding point of morphine in the mu-opioid receptor.     

The effects of acute and chronic morphine treatment and of morphine withdrawal on rat brain in vivo

1. The effects of morphine, nalorphine, acetazolamide, and 10% CO₂ on brain metabolite concentrations of 24h-starved rats were studied. 2. A single dose of morphine (20mg/kg body wt.) caused an increase in brain glucose concentration (42%) and decreased concentrations of lactate (24%), pyruvate (29%), citrate (20%), α-oxoglutarate (16%), malate (14%) and creatine phosphate (10%) after 30min. No changes were found in adenine nucleotide concentrations. 3. The same dose of morphine increased arterial CO₂ from 5.07 to 7.60 kN/m² (38 to 57 Torr), decreased the pH from 7.41 to 7.31 and decreased O₂ from 14.1 to 10.8kN/m² (106 to 81 Torr) at 30min. 4. Rats injected with morphine three times daily (20mg/kg body wt.) for 2 weeks had no changes in brain metabolite concentrations or in blood gases 30min after their last injection. 5. Nalorphine (an antagonist of morphine) caused essentially no changes in brain metabolite concentrations in normal rats. When nalorphine (20mg/kg) was administered to rats previously treated with morphine three times daily for 2 weeks, there was an increase in brain glucose (100%), lactate (23%), pyruvate (18%) and citrate (10%) concentrations. 6. Acetazolamide (an inhibitor of carbonic anhydrase) and 10% CO₂ increased the arterial CO₂ from 4.79 to 6.78kN/m² (36 to 51 Torr) and from 5.32 to 10.8kN/m² (40 to 81 Torr) respectively. 7. Both acetazolamide and 10% CO₂ caused changes in brain metabolite concentrations similar to those for acutely administered morphine. Thus 10% CO₂ caused increased brain glucose concentration (123%) and decreased brain lactate (46%), pyruvate (34%), citrate (26%), α-oxoglutarate (33%), malate (45%) and creatine phosphate (7%) concentrations. No changes in adenine nucleotide concentrations were found. 8. The results indicate that the effect of morphine on brain metabolite concentrations may be accounted for by the increased [CO₂]. 9. These findings constitute a consistent pattern of metabolic changes after acute morphine administration, morphine addiction, and withdrawal from morphine addiction.     

Endothelin receptor antagonists restore morphine analgesia in morphine tolerant rats

Several neurotransmitter mechanisms have been proposed to play a role in the development of morphine tolerance. The present study provides evidence for the first time that endothelin (ET) antagonists can restore morphine analgesia in morphine tolerant rats. Tolerance to morphine was induced by subcutaneous implantation of six morphine pellets during a 7-day period. The degree of tolerance to morphine was measured by determining analgesic response (tail-flick latency) and hyperthermic response to morphine sulfate (8 mg/kg, subcutaneously (s.c.)) in placebo and morphine pellet implanted rats. The maximal tail-flick latency in morphine pellet-vehicle treated rats (7.54 s) was significantly lower (P<0.05) when compared to placebo pellet-vehicle treated rats (10s), indicating that tolerance developed to the analgesic effect of morphine. In separate sets of experiments, ET antagonists, BQ123 (10 microg, intracerebroventricularly (i.c.v.)) and BMS182874 (50 microg, i.c.v.) were administered in placebo and morphine tolerant rats. BQ123 was injected twice daily for 7 days and once on day 8. BMS182874 was administered only on day 8. Morphine (8 mg/kg, s.c.) was administered 30min after BQ123 or BMS182874 administration. It was found that both BQ123 and BMS182874 potentiated morphine analgesia in placebo and morphine tolerant rats. BQ123 potentiated tail-flick latency by 30.0% in placebo tolerant rats and 94.5% in morphine tolerant rats compared to respective controls. BMS182874 potentiated tail-flick latency by 30.2% in placebo tolerant rats and 66.7% in morphine tolerant rats. Morphine-induced hyperthermic effect was also potentiated by BQ123 and BMS182874. The duration of analgesic action was also prolonged by BQ123 and BMS182874. The effect of BMS182874 was less as compared to BQ123. BQ123 and BMS182874 are selective ET(A) receptor antagonists. Therefore, it is concluded that ET(A) receptor antagonists restore morphine analgesia in morphine tolerant rats.     

Facilitation of spinal morphine analgesia in normal and morphine tolerant animals by neuropeptide SF and related peptides

Neuropeptide FF and related synthetic amidated peptides have been shown to elicit sustained anti-nociceptive responses and potently augment spinal anti-nociceptive actions of spinal morphine in tests of thermal and mechanical nociception. Recent studies have described the occurrence of another octapeptide, neuropeptide SF (NPSF) in the spinal cord and the cerebrospinal fluid and demonstrated its affinity for the NPFF receptors. This study examined the effects of NPSF and two putative precursor peptides, EFW-NPSF and NPAF, on the spinal actions of morphine in normal and opioid tolerant rats using the tailflick and pawpressure tests. In normal rats, NPSF demonstrated weak intrinsic activity but sub-effective doses of the peptide significantly increased the magnitude and duration of spinal morphine anti-nociception in both tests. A low-dose of NPSF also augmented the spinal actions of a delta receptor agonist, deltorphin. The morphine-potentiating effect of NPSF was shared by EFW-NPSF and the octadecapeptide NPAF. In animal rendered tolerant by continuous intrathecal infusion of morphine for 6 days, low dose NPSF itself elicited a significant anti-nociceptive response and potently increased morphine-induced response in both tests. In animals made tolerant by repeated injections of intrathecal morphine, administration of NPSF, EFW-NPSF, and NPAF with morphine reversed the loss of the anti-nociceptive effect and restored the agonist potency. The results demonstrate that in normal animals NPSF and related peptides exert strong potentiating effect on morphine anti-nociception at the spinal level and in tolerant animals these agents can reverse the loss of morphine potency.     

GABA in morphine analgesia and tolerance

Drugs affecting various steps of GABA transmission exhibit analgesia in a variety of experimental models in animals; this analgesic response generally requires high doses of the drugs and does not appear to be opiate-like since the GABAergic analgesia is naloxone-insensitive and lacks dependence liability. The outcome of the analgesia response is variable when opiate and GABAergic drugs are administered together; however, directly acting GABA receptor stimulants and GABA-transaminase inhibitors generally enhance the analgesic effect of opiates. The development of newer GABAergic drugs with greater potency and specificity may offer an alternative to opiate analgesics. The results obtained over the years, on the possible involvement of the GABA system in morphine tolerance and dependence are equivocal. Studies on region-specific changes in opiate-GABA interaction as well as opiate-GABA-benzodiazepine interaction are needed to further elucidate the role of GABA on opiate system.     

蛋白激酶C与吗啡耐受

蛋白激酶C(protein kinase C,PKC)属于AGC蛋白激酶家族(即PKA/PKG/PKC激酶家族),在吗啡介导的μ-阿片受体脱敏及吗啡耐受中具有重要作用,因此研究PKC的细胞信号传导机制对吗啡耐受的治疗具有重要的临床意义。本文综述了PKC在吗啡耐受中的作用。     

Strychnine, morphine and monamine depression

Strychnine has been applied by microiontophoresis to cells in the cerebral cortex of rats. On pyramidal tract cells no blockade of the suspected neurotransmitters noradrenaline, acetylcholine or 5-hydroxytryptamine was seen, but on nonpyramidal tract cells 25% of depressant responses to 5-hydroxytryptamine were reversibly antagonised by strychnine.Morphine has been tested similarly and has been shown not to interact with 5-hydroxytryptamine of noradrenaline.Strychnine has long been known as a convulsant alkaloid. Early neurophysiologists discovered that strychnine would cause high amplitude ‘spike’ discharges from the central nervous system (1), this being taken as the neural counterpart of strychnine seizures.Interest was therefore aroused by the report of Phillis &; York (2) that in the cerebral cortex strychnine, applied by microiontophoresis, could antagonise depressant responses to suspected monoamine transmitters. Doubt is cast on this finding by the results of several groups of workers (3, 4, 5, 6, 7), who have failed to demonstrate any reduction by strychnine of either neural or noradrenaline-induced inhibition.The present study was therefore undertaken to reinvestigate the effects of strychnine on depressant responses to acetylcholine, noradrenaline and 5-hydroxytryptamine when these agents were applied by microiontophoresis to spontaneously active cells in the rat cerebral cortex.The study also investigates the possibility of an interaction between morphine and monoamine depressions. Each of the three putative transmitters tested here has been implicated in morphine's analgesic and possibly addictive properties (8, 9, 10, 11) and morphine antagonism of 5-hydroxytryptamine in the periphery is well known (12).     

Enhancement of tolerance development to morphine in rats prenatally exposed to morphine,methadone, and buprenorphine

Background  

Abuse of addictive substances is a serious problem that has a significant impact on areas such as health, the economy, and public safety. Heroin use among young women of reproductive age has drawn much attention around the world. However, there is a lack of information on effects of prenatal exposure to opioids on their offspring. In this study, an animal model was established to study effects of prenatal exposure to opioids on offspring.     

Chronopharmacology of morphine in mice

Dosing-time-dependent changes in the effect and toxicity of morphine were examined in mice housed under alternating 12 h light (07:00 to 19:00 h) and dark (19:00 to 07:00 h) cycles. Morphine (0.5 mg/kg) was injected intraperitoneally (i.p.) in animals to assess its beneficial effect (i.e., protection against the kaolin-induced, bradykinin-mediated, writhing reaction) and its toxicity (i.e., alteration of the hepatic enzymes of aspartate aminotransferase [AST] alanine aminotransferase [ALT], and glutathione [GSH] in separate experiments). The magnitude of the analgesic effect of morphine depended on dosing time, with minimum effect at 02:00 h and maximum effect at 14:00 h. The serum hepatic enzyme levels of AST and ALT increased after dosing morphine (100 mg/kg) at 02:00 and 14:00 h. Time courses of these enzymes did not differ between the two trials. However, hepatic GSH, which is involved in the detoxification of chemical compounds, significantly decreased after i.p. morphine injection at 02:00 but not at 14:00 h. Overall, the results suggest that the analgesic effect of morphine is greater after dosing during the resting than during the activity phase of mice that have been induced with bradykinin-mediated pain. Drug-induced hepatic damage as inferred by GSH alteration, however, may be greater after dosing during the active phase.     

Rapid and highly automated determination of morphine and morphine glucuronides in plasma by on-line solid-phase extraction and column liquid chromatography

A high-performance liquid chromatography (HPLC) method has been developed for the determination of morphine and its main metabolites, morphine-6-glucuronide (M-6-G) and morphine-3-glucuronide (M-3-G), in plasma or cerebrospinal fluid. Samples were extracted using on-line solid-phase extraction followed by reversed-phase HPLC with fluorescence detection. Recoveries of 20 ng morphine and morphine glucuronides in plasma were over 95%. The limit of detection using 400 μl of a biological matrix was 0.85, 3.4 and 1.0 ng/ml of M-3-G, M-6-G and morphine, respectively. Inter- and intra-day assay precision was better than 10%. The main advantages of the present described method are increased recoveries (>95%) and a high degree of automation allowing a high speed in routine analysis. The time required for the fully automated analysis of one sample was less than 26 min.