جستجوی مقالات مرتبط با کلیدواژه « dependence » در نشریات گروه « پزشکی »

The orexinergic system and its receptors are involved in many physiological processes. Their functions in energy homeostasis, arousal, cognition, stress processing, endocrine functions, and pain modulation have been investigated. Many studies have shownthat the orexinergic system cooperates with the dopaminergic system in the addiction process. Emerging evidence suggests that the orexinergic system can be effective in the induction of drug dependence and tolerance. Therefore, several researches have been conducted on the effect of orexin receptor (OXR) antagonists on reducing tolerance and dependence caused by drug abuse. Due to the significant growth of the studies on the orexinergic system, the current literature was conducted to collect the findings of previous studies on orexin and its receptors in the induction of drug addiction. In addition, cellular and molecular mechanismsof the possible role of orexin in drug tolerance and dependence are discussed. The findings indicate that the administration ofOXR antagonists reduces drug dependence. OXR blockers seem to counteract the addictive effects of drugs through multiple mechanisms, such as preventing neuronal adaptation. This review proposes the potential clinical use of OXR antagonists in the treatment of drug dependence.

Research shows that -Pinene interacts with the opioidergic system.

This study aims to examine the toxicity and the effects of -Pinene on morphine tolerance and dependence in mice.

Guidelines No. 423 and No. 407 were used to investigate acute and sub-chronic toxicity, respectively. For sub-chronic toxicity analysis, the animals were sacrificed on day 28, and blood and tissue samples were collected. After inducing morphine tolerance or dependence, in both phases, animals received i.p. vehicle, diazepam(5 mg/kg), and-Pinene (3.125, 6.25, and12.5 mg/kg). Withdrawal signs were recorded for 30 minutes.

Only the acute dose of -Pinene showed mortality in animals, but mild lesions were seen in the brain, liver, and kidneys in the mice receiving its subchronic dose. Moreover, ALT, AST, ALP, and TG levels increased (P < 0.05) in female mice. Besides, 6.25 and 12.5 mg/kg (P < 0.001) of -Pinene and only its high dose (12.5 mg/kg) (P < 0.001) reduced the number of jumps in the tolerance and dependence phases, respectively. Diarrhea (P < 0.001), writhing (P < 0.001), rearing, and climbing (P < 0.05 and P < 0.001, respectively) behaviors decreased in the tolerance phase, and grooming, climbing, and teeth chattering declined in the dependence phase (P < 0.001).

The LD50 of -Pinene was lower than 2000 mg/kg, but its subchronic dose caused mild tissue toxicities and biochemical changes. Moreover,-Pinene decreased morphine tolerance and dependence and possibly was useful for the treatment of opioid dependence after complimentary trials.

Although a surge of interest in examining the co‐occurrence of problematic use of different technology means has recently emerged, findings are still inconclusive. This web-based survey aimed at examining whether (a) personality traits, coping strategies, and sociodemographics are associated with problematic use of the internet, smartphone, and SMS among Greek users and (b) personality traits mediate the relationship between maladaptive coping strategies and problematic use of the three media. Study design: A cross-sectional study.

A convenience and snowball sample of 1,016 participants (84.4% female, mean age 30.3 years) completed the Problematic Internet Use Questionnaire-9 (PIUQ-9), the Mobile Phone Problem Use Scale (MPPUS), the Self-Perception of Text Message Dependency Scale (STDS), the Personality Diagnostic Questionnaire 4+ (PDQ-4+), and the Brief Coping Orientation to Problems Experienced Inventory (COPE).

Shared predictors between the three problematic uses were younger age and low educational level, the coping strategy of substance use, and the narcissistic, avoidant, and dependent personality disorders. The coping strategies of self‒distraction and behavioral disengagement were common between the problematic users of the internet and smartphone. Schizoid traits predicted problematic smartphone users, paranoid traits predicted problematic internet users, and histrionic traits predicted problematic SMS users. Cluster C personality disorders fully mediated the relationship between maladaptive coping strategies and problematic use of technology-based tools, thus suggesting their amplifying role in this relationship.

Addressing shared factors between the three groups of problematic users, such as teaching adaptive coping strategies, should be the aim of effective and cost-saving treatment and preventive efforts.

 Opioids are the principal drugs of choice for managing acute severe pain; however, physical dependence is still reported as one of the main limiting factors in the clinical application of these drugs. In the present study, the effect of Ganoderma lucidum was assessed on morphine dependence in mice.

 A 19-day administration schedule was applied to induce morphine dependence in male adult NMRI mice. The mice were given intraperitoneal (i.p.) morphine sulfate once daily in an increasing dose of 10, 20, and 40 mg/kg. Then, G. lucidum hydroalcoholic extract (12.5, 25, and 50 mg/kg, i.p.) was given to the mice from days 10 to 18. Another group of mice received single doses of the extract (50, 100, and 200 mg/kg, i.p.) only on the 19th day. Naloxone (3 mg/kg, i.p.) was used to precipitate withdrawal syndrome. Normal saline and diazepam (0.25 mg/kg) were used as the negative and positive controls, respectively.

 The administration of single doses of G. lucidum extract (100 and 200 mg/kg, i.p.) significantly decreased the number of jumps, leanings, and diarrhea in mice subjected to morphine dependence. The repeated administration of G. lucidum extract (25 and 50 mg/kg for nine days) significantly attenuated the number of jumps, leanings, and diarrhea in morphine-dependent mice.

 Overall, G. lucidum extract attenuates induced morphine dependence and inhibits withdrawal syndrome symptoms in mice.

Kidney failure is a common public health problem around the world. The vast majority of kidney failure cases in Sub-Saharan African nations, including Ethiopia, go undetected and untreated, resulting in practically certain mortality cases. This study was aimed primarily to model the time to (right and left) kidneys failure in the patients at Adama Hospital Medical College using the copula model. Study design: A retrospective cohort study.

The copula model was used to examine join time to the right and left kidneys failure in the patients by specifying the dependence between the failure times. We employed Weibull, Gompertz, and Log-logistic marginal baseline distributions with Clayton, Gumbel, and Joe Archimedean copula families.

This research comprised a total of 431 patients, out of which, 170 (39.4%) of the total patients failed at least one kidney during the follow-up period. Factors such as sex, age, family history of kidney disease, diabetes mellitus, hypertension, and obesity were found to be the most predictive variables for kidney failure in the patients. There was a 41 percent correlation between the patients’ time to the right and left kidneys failure.

The patients’ kidney failure risk factors included being a male, older adult, obese, hypertensive, diabetic and also having a family history of kidney disease. The dependence between the patient’s time to the right and left kidneys failure was strong. The best statistical model for describing the kidney failure datasets was the log-logistic-Clayton Archimedean copula model.

Glaucoma is a worldwide problem that causes vision loss and even blindness, with a prevalence rate ranging from 1.9% to 15%. In Ethiopia, glaucoma is the fifth cause of blindness. This study aimed to explore the dependence between blindness of the right and the left eyes of glaucoma patients and assess the effects of the covariates under the dependence structure. Study Design: A retrospective cohort study.

The study population included the glaucoma patients at Alert hospital from January 1, 2018, to December 30, 2021. The copula model was used to estimate the time to the blindness of the right and the left eyes of the glaucoma patients by specifying the dependence between the event times.

Out of 537 glaucoma patients, 224 (41.71%) became blind at least in one eye during the follow-up period. The results of the Clayton copula model revealed that factors, such as age, residence, diabetes mellitus, stage of glaucoma, and hypertension are considered the most prognostic factors for blindness in glaucoma patients. The findings also revealed that there was a strong dependence between the time to the blindness of the right and the left eyes in the glaucoma patients (τ = 0.43).

Based on the obtained results, high age, urban residence, hypertension, diabetes mellitus, and higher stage of glaucoma were factors associated with time to the blindness in the glaucoma patients. There was also a dependence between the right and the left eyes of the glaucoma patients. The results revealed that the Clayton Archimedean copula model was the best statistical model for accurate description of glaucoma patients’ datasets.

Numerous attempts have been made to decrease the incidence of opioid dependence after orthopedic surgeries. However, no effective means of preoperative risk stratification currently exists. The purpose of this study was to determine the ability of the Opioid Risk Tool (ORT) to predict the rate of opioid dependence 2 years after arthroscopic rotator cuff repair (ARCR).

We prospectively evaluated all patients undergoing primary ARCR at a single institution over a 1.5 year period with a minimum of 2-year follow-up. All patients completed the ORT prior to surgery and were stratified into Low, Moderate, and High risk categories. The primary outcome was postoperative opioid dependence, defined as receiving a minimum of 6 opioid prescriptions within 2 years following surgery. Secondary outcomes included the total number of morphine milligram equivalents prescribed, total number of opioid prescriptions filled, and total number of opioid pills prescribed during this time interval. All outcome variables were compared amongst Low, Moderate, and High risk groups. Assessment of a statistical correlation between each outcome variable and individual numerical ORT scores (1-9) was performed.

A total of 137 patients were included for analysis. No statistically significant difference was noted in any primary or secondary outcome variable when compared between Low, Moderate, and High risk groups. The total cohort demonstrated a 19% rate of post-operative opioid dependence. No correlation was identified between any outcome variable and individual numerical ORT scores. A greater rate of dependence and quantity of opioids prescribed was noted amongst patients with a history of prior opioid use.

The ORT was not predictive of the risk of opioid dependence or quantity of opioids prescribed after ARCR. Attention should be focused on alternative means of identification and management of patients at risk for opioid dependence after orthopedic procedures, including those with a history of prior opioid use. Level of evidence: III

Atorvastatin exerts neuroprotective effects on the treatment of central nervous system disorders. Morphine analgesic tolerance and dependence remain as major concerns in medicine. Nitric oxide (NO) pathway mediates the development of opioid analgesic tolerance and dependence, as well as atorvastatin neuroprotection.

The present study aimed to assess the possible involvement of the NO/cGMP pathway in the process of the effects of atorvastatin on morphine physical dependence.

Dependence was induced by repetitive injection of morphine sulfate. Naloxone was injected at the dose of 4 mg/kg on the last day of the experiment to assess withdrawal signs. Animals received atorvastatin (1, 5, 10, and 20 mg/kg, orally). Nitric oxide synthase (NOS) inhibitors and ODQ were injected before protective dose of atorvastatin. The gene expression of NOS isoforms was evaluated by real-time PCR. Thereafter, the hippocampal levels of cGMP and nitrite were measured.

Treatment with atorvastatin 10 mg/kg significantly attenuated naloxone-induced withdrawal behaviours. The administration of L-NAME, aminoguanidine, and ODQ before atorvastatin enhanced its effects. The treatment with atorvastatin significantly decreased the nitrite and cGMP levels as well as NOS gene expression in the hippocampus of dependent animals.

It can be concluded that atorvastatin, possibly, through inducible NOS, could alleviate morphine dependence and withdrawal signs.

Opioids use has been limited due to tolerance and dependence as major unwanted effects. Previous evidence has shown that targeting endocannabinoid signaling can prevent the development of opioid tolerance and dependence. This study was designed to evaluate the effect of phenylmethylsulfonyl fluoride (PMSF), an inhibitor of fatty acid amide hydrolase (FAAH), on morphine antinociceptive tolerance and physical dependence in mice. The antinociceptive effects of PMSF at the doses 60, 120, and 300 mg/kg were investigated. Results showed that PMSF has a notable antinociceptive effect at doses 120 and 300 mg/kg. The dose of (60 mg/kg, i.p.) PMSF was considered as a sub-antinociceptive dose. Morphine tolerance and dependence were induced by twice-daily injection of morphine (10 mg/kg, s.c.) for 10 consecutive days and the last dose on day 11. Tolerance was assessed by the hot-plate test and dependence by naloxone-precipitated morphine withdrawal signs. In the brain, oxidative stress markers include activities of glutathione peroxidase, catalase, superoxide dismutase, and levels of malondialdehyde and glutathione were determined. A sub-antinociceptive dose (60 mg/kg) of PMSF could reduce tolerance in both acute and chronic methods of administration. However, alleviation of dependence and suppression of oxidative stress markers occurred in the chronic administration of PMSF. In conclusion, it seems that PMSF can suppress morphine tolerance and dependence. However, more studies are needed to clarify its mechanism.

It is well known that the majority of good grade (WFNS I and II) patients who undergo microsurgical clipping achieve a favorable outcome, but still a number of patients who are independent before surgery face unfavorable outcomes signifying the impact of microsurgical clipping. The aim of this study was to quantify the risk of dependency in patients who had no previous neurological deficit.

We reviewed 50 consecutive good grade patients with ruptured anterior circulation aneurysms who underwent microsurgical clipping between May 2017 and May 2020 in the Department of Neurosurgery, Punjab Institute of Neurosciences, Lahore. The clinical outcome at discharge and at 3 months follow-up was assessed using the Glasgow Outcome Scale (GOS).

In this study, seven patients (14%) were dependent (GOS II and III) following clipping. Out of this, five patients (10%) suffered surgical insult in the form of intraoperative rupture (4%), postop infarct (4%), and direct brain damage (2%).

Patients without neuro deficit preoperatively still suffer unfavorable outcome mainly due to operative insults. Vascular injuries remain the main cause of morbidity producing dependency. Therefore, it is essential to reiterate that all surgical techniques must be directed at minimizing the risk to vessels, both during dissection and at clip placement.

The inflammatory system, oxidative stress, and cholinergic pathways are some important factors in long-term opioid dependence withdrawal. The adverse effects of some adjunctive medications on withdrawal symptoms treatment limit their clinical efficiency and finding compounds with inhibitory effects on opioid dependence can be helpful. The antioxidant, antinociceptive, and anti-inflammatory properties of Satureja khuzestanica extract (SKE) have been noted. Additionally, itcould reduce morphine analgesic tolerance. Given that no study has assessed the effect of SKE on morphine-induced withdrawal symptoms, we have tried to investigate it in this study.

Male Wistar rats were used in this study. The rats were treated with morphine for 7 days. The control group received saline, and intervention groups received SKE intragastrically by gavage (100 mg/kg, 50 mg/kg, and 25 mg/kg) 15 minutes before morphine injections. Five hours after the last injection, naloxone was used and withdrawal symptoms were assessed for one hour. SPSS software version 16.0 was used for statistical analysis, and P≤0.05 was considered statistically significant.

SKE diminished weight loss and jumping (P≤0.001). It decreased grooming behaviors and cramps (P≤0.01). SKE was found to decrease morphine withdrawal symptoms and 100 mg/kg was the most effective dose. Additionally, different doses of SKE were able to eliminate ptosis, diarrhea, and teeth chattering in animals; however, different doses had different effects on withdrawal symptoms.

Naloxone significantly increased the frequency of jumping, cramps, weight loss, grooming, and induced ptosis, diarrhea, and teeth chattering. Treatment with SKE can significantly reduce morphine withdrawal symptoms. This can be done through its ability to decrease inflammation

Co-occurring methamphetamine (METH) use during methadone maintenance therapy (MMT) is a highly prevalent and progressive problem in Iran. There are no registered pharmacological treatments for treating METH use disorder. The present study investigates the potential efficacy of atomoxetine in the treatment of these patients.

In a double-blind, controlled clinical trial, 86 METH-dependents on MMT randomly received either atomoxetine (40 mg/d) or placebo. We measured the craving scores with visual analog scale (VAS) on a weekly basis, and evaluated depression, anxiety and stress with the Depression Anxiety Stress Scales (DASS) on a monthly basis. Measurements were made in each weekly visit with urinary METH drug test.

Atomoxetine significantly reduced METH craving (P < 0.001). Negative METH urine test increased significantly in the drug group compared to the placebo group (P = 0.007). While initially the METH urine test was positive for all patients, 56% (25/45) in the atomoxetine group and 26% (11/41) in the placebo group had negative METH urine tests after 8 weeks. DASS were decreased in both groups with a greater reduction in the atomoxetine group [depression (P = 0.028), anxiety (P = 0.038), and stress (P = 0.031)]. Only mild side effects were observed.

This study confirms the safety and clinical tolerance of atomoxetine, and its appropriate efficacy in suppressing METH craving and possible potential effects on its treatment.

Ventral Tegmental Area (VTA) is a core region of the brainstem that contributes to different vital bio-responses such as pain and addiction. The Dopaminergic (DA) cellular content of VTA has major roles in different functions. This study aims to evaluate the cellular effect of tramadol on the putative VTA-DA neurons. Wistar rats were assigned into three groups of control, sham, and tramadol-treated. The animals were anesthetized and their VTA-DA neuronal activity was obtained under controlled stereotaxic operation. The firing rate of the neurons was extracted according to principal component analysis by Igor Pro software and analyzed statistically considering P<0.05 as significant. Tramadol (20 mg/kg) was infused intraperitoneally.  Overall, 121 putative VTA-DA neurons were isolated from all groups. In tramadol-treated rats, the inhibition of the neuronal firing was proposed as tolerance and the excitation period as dependence or withdrawal. The Mean±SD inhibition time lasted up to 50.34±10.17 minutes and 31% of neurons stopped firing and silenced after 24±3 min on average but the remaining neurons lowered their firing up to 43% to 67% of their baseline firing. All neurons showed the excitation period, lasted about 56.12±15.30 min, and the firing of neurons increased from 176% to 244% of their baseline or pre-injection period. The tolerance and dependence effects of tramadol are related to the changes in the neuronal firing rate at the putative VTA-DA neurons. The acute injection of tramadol can initiate neuroadaptation on the opioid and non-opioid neurotransmission to mediate these effects.

Long-term exposure to opioids may lead to physical dependence and tolerance. The purpose of this study was to investigate the effects of Citrus aurantium essential oil (CEO) on the morphine-induced tolerance and dependence. To evaluate morphine tolerance, the experiments were carried out in 6 rat groups (n=8) in the weight range of 225-275 g. The control group received morphine (10 mg/kg/day) and the test groups received morphine with the different doses of essential oil (CEO 20, 40 and 80 mg/kg/day) or 4 mL/kg of essential oil vehicle (KolliphorÒ HS15 30% in normal saline that adjusted in pH=7.4 with phosphate buffer) intraperitoneally. The hot-plate test was carried out every other day, 90 minutes after the injections. To examine morphine withdrawal, male Wistar rats were divided into seven groups (n=8) randomly, including: morphine sulphate, CEO (20, 40 and 80 mg/kg) + morphine, vehicle of CEO + morphine. The rats were rendered morphine-dependent by injection of additive doses of morphine subcutaneously for 9 days. The procedure of the morphine administration was as following protocol: day1: 5 mg/kg/12h, day 2 and 3: 10 mg/kg/12h, day 4 and 5: 15 mg/kg/12h, day 6 and 7: 20 mg/kg/12h and day 8 and 9: 25 mg/kg/12h. In the 9th day, 2 hours after the last dose of morphine, naloxone (4 mg/kg) was injected intraperitoneally. Some withdrawal behaviors were counted for 60 minutes. Morphine tolerance was completed after 5 days in the control group. The vehicle group showed tolerance on the 9th day (p-value=0.991), 20mg group in the 13th day (p-value to control=0.010, to vehicle=0.049), 40 mg group on the 15th day (p-value to control and vehicle<0.001) and 80 mg group on the 13th day (p-value to control= 0.001, to vehicle= 0.007). The results showed that CEO could reduce the morphine withdrawal syndrome and total withdrawal score (TWS). Intraperitoneally injection of CEO in two doses (40 mg/kg with p<0.001 and 80 mg/kg with p<0.01) significantly reduced the TWS in comparison to the morphine+vehicle treated group. The results indicated that chronic administration of C. aurantium essential oil extracted had beneficial effects in reducing morphine withdrawal syndrome and could significantly delay tolerance to morphine.