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Based on the numerous pieces of evidence regarding the role of opioids in immune function, viral replication, and virus-mediated pathology, we decided to assess the incidence and severity of COVID outcomes in people undergoing opioid maintenance treatment. Methods: This is a prospective, descriptive, multi-center study that included patients undergoing maintenance treatment in opioid agonist treatment OAT clinics in different cities of Iran. Demographic information, underlying disease, history of maintenance treatment, type of drug used, history of addiction, smoking, and the kind of substance abused, were recorded. A physician evaluated the COVID symptoms, and the severity of the disease was defined based on the number of observed symptoms. Results: The results have not shown any significant difference in the severity of COVID symptoms in different nationalities, gender, and treatment groups. Furthermore, the history of drug abuse, including time and type of abuse and smoking, has not indicated any significant association with the occurrence of symptoms. Conclusion: Our results have demonstrated that the severity of symptoms in people with the underlying disease was significantly higher than in others. But there is no association between sex, race, treatment groups, and abuse history with the severity of COVID symptoms in methadone maintenance treatment MMT patients. Opioid receptors are G protein-linked receptors located in the nervous system, kidney, spleen, liver, intestine, and lung. Also, opioid receptors are distributed in the immune cells such as lymphocytes, macrophages, neutrophils, and monocytes Wang, Recent studies have shown that opioids have immunomodulatory and anti-inflammatory effects by influencing immune cell function. Effects of opioids on immune functions include downregulation of natural killer cells and T cell activities, depression of phagocytic activity of neutrophils and macrophages; affecting cytokine receptor expression Finley et al. The alkaloid of morphinane in opioids, through lysosomotropic properties, inhibits viral uncoating and the entrance of coronavirus Cismaru et al. Moreover, opioids are effective in palliating dyspnea and limiting hyperventilation by decreasing respiratory drive and corollary discharge, altering the activity of lung opioid receptors, and having anxiolytic effects Mahler, Lymphopenia, lymphocyte dysfunction, granulocyte and monocyte abnormalities, high cytokine levels, and increased total antibodies are present in COVID patients Yang et al. Two major pathways of COVID transmission to people are respiratory droplets and face-to-face contact. Headache, loss of taste or smell, diarrhea, nausea, fatigue, etc. It seems that the mortality rate can be increased due to underlying disorders like diabetes and cancer Nouri-Vaskeh et al. Coronavirus is known to have four primary structural proteins: nucleocapsid proteins, envelope, membrane, and spike. The spike helps the coronavirus to enter the host cell Li et al. After the first exposure, cytotoxic cells, antibodies, and interferons trigger the immune system. Alveolar infiltration of T cells, macrophages, and neutrophils occurs in the advanced levels of the disease Khadke et al. While attempting to provide therapies for patients with COVID, many treatments have been tested which often resulted in controversial consequences Senefeld et al. Some studies have indicated that opioid receptors have immunomodulatory effects. The type of virus determines the effects of the opioid system on human viral infections. The opioid system may enhance or suppress viral pathogenesis by altering host immune responses Wang X. On the contrary, it has a beneficial role in the outcome of respiratory viral diseases such as influenza virus and respiratory syncytial virus and could serve as effective therapeutic targets Tahamtan et al. Despite the use of these medications in the clinic, their role in the consequences of viral respiratory diseases has not yet been studied in detail. Due to the lack of studies related to the effectiveness of opioids in patients with COVID, we attempted to collect and provide some helpful information about the possible protective effects of this category of medications by evaluating patients referred to methadone maintenance treatment centers and following them up in terms of incidence, severity, and incidence of symptoms. This is a prospective, descriptive, multi-center study that included patients undergoing maintenance treatment in opioid agonist treatment OAT clinics in Tehran, Qom, Khorasan, Esfahan, and Kashan cities of Iran. Sampling was performed through the Census method. All the patients eligible for the study patients with observance of the principles of confidentiality, honesty, the confidentiality of information, etc. Demographic information age, gender, and body mass index , underlying diseases diabetes, hypertension, heart failure, and chronic kidney disease , history of maintenance treatments, type of drugs used, history of addiction, smoking, and the kind of substance abused, were extracted from patient statements and files. Based on a checklist, including cough, fever, myalgia, headache, dyspnea, diarrhea, and loss of taste or smell, all the symptoms were recorded. Finally, the severity of the disease was evaluated in the mentioned period. We analyzed collected data every 3 months and presented it as the first follow-up: the first trimester of study; second follow-up: the second trimester of study, in this group of patients. Furthermore, the hospitalization rate and mortality were recorded during the study Figure 1. The SPSS statistical software version The remaining parameters e. During the study period, patients were enrolled in this research. The median age was Table 1 shows the demographic characteristics of those who entered the study. The underlying disease and medication history of patients have summarized in Table 2. Heart disease 6. TABLE 2. Disease and medication history of patients referred to MMT centers. The prevalence of COVID symptoms in the second trimester of the study period second follow-up was higher among patients than in the first trimester first follow-up Table 3. During a 6-month study duration, 4 0. The debate on whether opioids could help to improve or prevent COVID has arisen since the beginning of the outbreak of this pandemic. So, we decided to investigate the incidence of symptoms and hospitalization in patients undergoing opioid maintenance therapy. Opioid agonist medications, including methadone, buprenorphine, and opium, have been administered at a specialized addiction clinic in Iran to treat opioid use disorder OUD. In this study, the incidence rate of clinical symptom due to COVID-9 in patients undergoing different maintenance therapy treatment have not shown any significant difference. Salimi et al. Other clinical and experimental studies also have indicated that opioid receptor signaling has a potentially beneficial role in the outcome of respiratory viral disease. In influenza and respiratory syncytial viruses RSVs , opioids reduce the rate and severity of infection through anti-inflammatory and immunomodulatory functions Salimi et al. Cismaru et al. So, oxycodone, hydromorphone fentanyl dihydrocodeine, diamorphine, and oral or parenteral morphine can be used for this purpose. Maher et al. Stimulating opioid receptors reduce mucus secretion in the respiratory system Krajnik et al. They also play a significant role in immune system activity, including antibody production, lymphocyte proliferation, and modulation of cytokine production. Furthermore, Opioids suppress IL6 signaling pathways Eisenstein, De Wilde et al. On the other hand, El-Hage et al. Furthermore, morphine enhances the severity of primary herpes virus infection Mojadadi et al. Since using opioids is known to have immunosuppressive effects, infection due to the novel coronavirus disease has been one of the major concerns in people using opioids during the pandemic. It is also worth mentioning that compared to non-users, higher mortality is recorded among opioid users Ao et al. In a study regarding long-term opioid therapy in patients, it was stated that due to compromised respiratory and immune function, susceptibility to COVID infection increases. It was also reported that the risk of mortality and morbidity increases in these patients Tuan et al. Therefore, all aspects should be weighed before using opioids to treat an inflammatory viral respiratory infection, and caution is required. Numerous studies have demonstrated the anti-inflammatory and immunomodulatory effects of opioids and the presence of opioid peptides in immune cells to reduce inflammatory hyperalgesia Machelska and Celik, It has also been shown that immune factors are significantly reduced after exposure of consumers drug users, healthy human subjects, and animal models to opioid compounds Roy et al. However, this immunosuppression efficacy cannot be generalized to all opioid compounds. Just morphine, fentanyl, and remifentanil have immunosuppressive effects, and other compounds such as tramadol and buprenorphine have neutral impacts on the immunity system. Animal studies have shown a suppressive effect of methadone, but clinical studies as maintenance therapy in heroin-addicted patients have indicated immune function restoration Franchi et al. Ghafari et al. However, Small sample sizes pose challenges to any statistical analyses. Many studies have demonstrated that older age, male sex, race mainly Black, Hispanic, and South Asian , and underlying comorbidities have been associated with disease severity or death of COVID patients Attaway et al. Our results also have shown that the severity of symptoms in people with the underlying diseases was significantly different from others. The limitation of this study was the lack of a control group do not consume any opioid compounds to investigate the relationship between opioid use and COVID outcomes. Therefore, large-scale studies in different ethnic and geographical groups are needed to evaluate the relationship between opioids and survival in COVID and clarify the effects of opioids on the clinical prognosis of COVID patients. Therefore, it is suggested that studies be conducted to investigate how opioid use may impact immunity in the lungs and alter viral replication and virus-mediated pathology in COVID We also did not have complete information on the mortality rate of patients in light centers in the same period of previous years to estimate excess mortality associated with COVID Another limitation of this study was the lack of accompanying patients to complete laboratory tests and chest CTs. Therefore, the complete laboratory data was not available to the researchers for analysis. Finally, more research needs to be done to determine if opioid administration can be helpful in viral diseases, specially COVID, or not. Furthermore, opioid addiction and misuse should be considered, and the potential benefits and harms during treatment should be weighed. Considering that the anti-inflammatory and immunomodulatory effects of opioids have been demonstrated in numerous studies, we decided to investigate the incidence of symptoms and hospitalization in patients undergoing opioid maintenance therapy. Our results have indicated that the severity of symptoms in people with the underlying disease was significantly higher than in other patients who did not have any underlying disease. But sex, race, treatment groups, and abuse history did not have any significant association with the severity of COVID symptoms in methadone maintenance treatment MMT patients. The raw data supporting the conclusion of this article will be made available by the authors, without undue reservation. Study concept and design: SK. Critical revision of the manuscript for important intellectual content: SH and JT. Study supervision: SH. We thank patients and clinicians of MMT clinics who participated in this research. We particularly acknowledge the assistance of Dr. Mohammad Abdekhoda and Dr. Narges Gholami; managers of substance abuse treatment center. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Ao, G. Attaway, A. Severe Covid pneumonia: Pathogenesis and clinical management. BMJ , n Chen, N. Epidemiological and clinical characteristics of 99 cases of novel coronavirus pneumonia in wuhan, China: A descriptive study. Lancet , — Cismaru, C. Multiple potential targets of opioids in the treatment of acute respiratory distress syndrome from COVID Corman, V. Euro Surveill. De Wilde, A. Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East respiratory syndrome coronavirus replication in cell culture. Agents Chemother. Eisenstein, T. The role of opioid receptors in immune system function. El-Hage, N. HIV-1 coinfection and morphine coexposure severely dysregulate hepatitis C virus-induced hepatic proinflammatory cytokine release and free radical production: Increased pathogenesis coincides with uncoordinated host defenses. Feng, Y. Current research on opioid receptor function. Drug Targets 13 2 , — Finley, M. Opioid and nociceptin receptors regulate cytokine and cytokine receptor expression. Franchi, S. Do all opioid drugs share the same immunomodulatory properties? A review from animal and human studies. Ghafari, M. Grass, G. How, with whom and when: An overview of cdmediated regulatory networks influencing matrix metalloproteinase activity. Huang, C. Clinical features of patients infected with novel coronavirus in Wuhan, China. Jia, H. ACE2 receptor expression and severe acute respiratory syndrome coronavirus infection depend on differentiation of human airway epithelia. Khadke, S. Harnessing the immune system to overcome cytokine storm and reduce viral load in COVID A review of the phases of illness and therapeutic agents. Krajnik, M. Opioid receptor bronchial tree: Current science. Care 8 3 , — Lechien, J. Intern Med. Li, W. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature , — Machelska, H. Opioid receptors in immune and glial cells—Implications for pain control. Maher, D. Suppression of human natural killer cells by different classes of opioids. Mahler, D. Opioids for refractory dyspnea. Opioids Refract. Matsunaga, M. Brain Behav. Mojadadi, S. Nouri-Vaskeh, M. Comparison of losartan and amlodipine effects on the outcomes of patient with COVID and primary hypertension: A randomised clinical trial. Rezaee, H. Roy, S. Opioid drug abuse and modulation of immune function: Consequences in the susceptibility to opportunistic infections. Neuroimmune Pharmacol. Rubin, E. Medical journals and the nCoV outbreak. Salimi, V. Opioid receptors control viral replication in the airways. Care Med. Senefeld, J. COVID convalescent plasma for the treatment of immunocompromised patients: A systematic review and meta-analysis. JAMA Netw. Open 6 1 , e Tahamtan, A. Opioids and viral infections: A double-edged sword. Tuan, W. BMJ Open 11 11 , e Wang, J. Morphine impairs host innate immune response and increases susceptibility to Streptococcus pneumoniae lung infection. Wang, S. Historical review: Opiate addiction and opioid receptors. Cell Transpl. Wang, X. Yang, L. Signal Transduct. Target Ther. The use, distribution or reproduction in other forums is permitted, provided the original author s and the copyright owner s are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher. Top bar navigation. About us About us. Sections Sections. About journal About journal. Article types Author guidelines Editor guidelines Publishing fees Submission checklist Contact editorial office. Drugs Outcomes Research and Policies. Materials and methods This is a prospective, descriptive, multi-center study that included patients undergoing maintenance treatment in opioid agonist treatment OAT clinics in Tehran, Qom, Khorasan, Esfahan, and Kashan cities of Iran. Flow diagram of participants through the study. TABLE 1. Demographic information of patients referred to MMT centers. TABLE 3. Clinical symptoms of patients referred to MMT centers. Edited by: Grigorios L.

A Review Study of Substance Abuse Status in High School Students, Isfahan, Iran

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Drug trafficking and fast growing drug distribution systems made the drug abuse as a global health problem. The illicit use of opiates contributes to the global burden of diseases resulting in premature disabilities and even death while it is increasing in all countries, especially in the developing countries such as Iran. Drug use is associated with physical dependency, socioeconomic complications, and other significant morbidity and mortality related infectious such as HIV 5 , 6. For the first time in , methadone was used as a replacement therapy for heroin dependency in New York 7. Since methadone can be used to treat opioid dependence, it is the preferred medication for drug detoxification worldwide. Addiction symptoms are dissolved in addicts who are on methadone therapy; however, after a chronic administration of methadone, sudden cessation causes a milder, albeit longer in duration, withdrawal syndrome compared with morphine cessation 8. Although more than 3 decades experience in opioid pharmacotherapy as methadone maintenance treatment MMT was successful in reducing losses, injuries, and drug related death 9 , 10 , although in recently published systematic reviews, the ability of MMT in mortality reduction has not been proved In summary, adverse effects of MMT is included by uncontrolled use and risk of accidentally ingestion which led to poisoning and the benefits are craving reduction for opiums especially heroin and in following protection against criminal activity or HIV infection 8 , Because of cultural, social, and geographical differences in Iranian drug abuser, the current study aimed to retrospective assessment of typical features of corpses due to opium intoxication including those on MMT in Isfahan, Iran, during a 6-year period. The current epidemiological retrospective, cross sectional study was done during a 6-year period in Isfahan, Iran. In the present study, all opioid-related death including the ones on MMT and overdose death cases intoxication corpses referred to the forensics center, affiliated to the Iranian ministry of health and medical education, from March to March were reviewed. Deaths due to accident, crime, poisoning, suicide, occupational illness or medical procedures are always investigated by a forensic pathologist. All post-mortem toxicology samples taken at autopsy are analyzed in forensic laboratory. Data extracted from the forensic center records included autopsy reports, toxicological analyses, hospital notes, death investigation, police reports, and demographic information were collected. Data on methadone treatment were obtained from the MMT statistics unit at the department of ministry of health in Isfahan. Information of corpses recorded in checklists contained age, gender, marital status single, married, divorced, or widow , job status self-employed, labor, clerk, military personnel, student, housekeeper, unemployed, soldier, driver, retired , educational status illiterate, preprimary school, middle school, high school, higher education, unknown , any history of self-injury and suicidal behaviors, where death occurred home, prison, work, street, others , the way of drug consumption injection, inhalation, eating, unknown , smoking, alcohol use, benzodiazepine and tricyclic anti-depressant abuse, and the type of opioid. Corpses not being autopsied, unidentified bodies, and those without toxicological reports were excluded. Also, the bodies transferred from other cities to the studied center were not enrolled. The possible association between various factors was assessed by multivariate logistic regression. P values less than 0. A total of cases of opioid overdose death were recorded. For clarification, 93, , , , , cases respectively were recorded from to As shown in Table 1 , the most deaths occurred in it was cases. During the study, males The youngest and oldest cases were 4 and 89 years old reported in and , respectively; 6. According to the results, most of the bodies were found at home. The frequencies of death due to drug injection overdose from to were Chronic hepatitis was found in There was a significant correlation between chronic hepatitis and gender, and opium use. Death from opioid overdose possesses an emerging public health problem in Iran 3. The present evaluation demonstrated that although drug overdose death was high during till , the rate remains stable. The demographic characteristics of corpses were assimilate to worldwide records, predominantly male, aged on average in their 30s, and drugs injectors 1. The current study is the first report describing the basic demographic and toxicological data on drug overdose death in Isfahan, Iran, from to Overdose risks in Isfahan vary among demographic groups, were the highest rates belong to people aged 20 - 40 years, male, with lower familial support. Unfortunately, the subgroup of 20 - 40 years old was most susceptible to drug abuse. Based on these results, it seems that in Iran younger ages are at greatest risk for addiction and related death. It should be considered in future policies and decision-making of the state system. On the other hand, most of corpses were unmarried, with lower level of education and income. Consistent with earlier studies in Iran, the reported demographic results were similar 13 - 15 , except in marriage state Based on the findings, job opportunities should be provided, if mortality reduction is desired by the officials Occupation is very important for the development upon career trajectory. Binswanger et al. Many affected cases in the current study were unemployed or self-employed. Similar to the other studies 14 , 15 , in the current study Different fate might be happened if earlier and timely medical care was applied. Toxicological assessments in the current study contained morphine, methadone, codeine, opium, alcohol, amphetamine compounds, commonly abused drugs such as benzodiazepines , and other poisons. It is noteworthy that toxicological analyses of stomach contents were positive for morphine, codeine, or opium. However, in recent papers published in Iran, methadone was the most common consumed drugs, followed by opium 14 , On the other hand, some other studies reported heroin as the first overdosed drug Horvath et al. The difference was predictable due to the number of addicts on MMT. In Isfahan, a growing trend was observed in cooperation with MMT program from to This trend showed a high popularity of MMT among addicts. But, according to the toxicological analyses, 99 bodies were positive for methadone overdose, while more than Due to the synergism effects of these substances on depression of respiratory, and cardiovascular system, it is essential to inform addict person above hazardous issue. In autopsy investigations, lung and liver were the most affected organs. Rate of changes reflecting chronic hepatitis in the liver of bodies was remarkably high We found that pulmonary edema, a common complication of opioid, in It was similar to the finding of other reports in Iran In analyses of multivalent regression, the relationship between different factors age, gender, type of drugs, positive test results for alcohol, benzodiazepines, and antidepressants and pathologic findings was investigated. It is predictable because high risks behaviors resulted in hepatitis are more common in males. The study found that non-injecting traditional drugs such as opium led to less exposure to hepatitis than industrial drugs crack, heroin, morphine, etc. Many of such involvements develop over the years after a long period of drug abuse. However, it is prevalent in older ages than youth. Although the current epidemiological study has lots of valuable information, it also has some limitations. It is better to consider cultural factors in a wider time span. Victims should be assessed for psychiatric conditions and its role should also be modulated by other factors in logistic regression. Finally, to combat addiction epidemic, firstly, we must accept thehigh prevalence instead of denying in our country. Off note, criminal justice policies should be adjusted, and treatment of drug users should be considered more seriously. According to the current study findings, the low-educated and low-income young males were the most high-risk population for drug overdose deaths in Iran. Finally, the essential role of education and job creation policies to prevent addiction was clarified. Drug Alcohol Depend. Bird SM. Over drugs-related deaths and , opiate-user-years of follow-up: Relative risks by sex and age group. Addiction Res Theory. Calabrese J. Iran's War on Drugs: Holding the Line? The Middle East Institute; Board INC. Report of the international narcotics control board for New York. New York; An Overview of Iran drug treatment and harm reduction programs. Textbook of addiction treatment. International Perspectives; Opium consumption and the risk of traffic injuries in regular users: a case-crossover study in an emergency department. Traffic Inj Prev. Barnett PG. Comparison of costs and utilization among buprenorphine and methadone patients. Bart G. Maintenance medication for opiate addiction: the foundation of recovery. J Addict Dis. Drug-related mortality and its impact on adult mortality in eight European countries. Eur J Public Health. Mortality prior to, during and after opioid maintenance treatment OMT : a national prospective cross-registry study. An overview of systematic reviews of the effectiveness of opiate maintenance therapies: available evidence to inform clinical practice and research. J Subst Abuse Treat. Eyes wide shut? Eur Addict Res. Prescription opioid mortality trends in New York City, examining the emergence of an epidemic. Hejazi AZ, Zeidabadinejad M. Shakeri epidemiological study of mortality rate from opioid abuse in referential bodies to khorasan department of forensic medicine Persian. Epidemiological study of mortality rate from opioid abuse in referential bodies to mazandaran department of forensic medicine in Persian. Mazandaran Univ Med Sci. Return to drug use and overdose after release from prison: a qualitative study of risk and protective factors. Addict Sci Clin Pract. Deadly heroin or the death of heroin -- overdoses caused by illicit drugs of abuse in Budapest, Hungary between and Neuropsychopharmacol Hung. General principles of care in toxicology and emergency medicine. We use cookies to provide you with the best possible experience. They also allow us to analyze user behavior in order to constantly improve the website for you. Abstract Background: Opioid use makes the largest contribution to drug abuse mortality, while it is increasing in the world, especially in Iran. Objectives: The current study aimed at obtain the typical features of corpses under methadone maintenance treatment MMT and opium intoxication in Isfahan, Iran. Patients and Methods: The current cross sectional study was conducted on opioid overdose deaths from March to March ; data on drug overdose death in forensic center affiliated to Iranian ministry of health and medical education were recorded by checklist. Results: Most of the opioid corpses were young They had low income, low education and were found at home; injection was the most common way of drug abuse In toxicological findings, morphine was the most common drug and more than Pulmonary edema was the most common pathological finding. Conclusions: According to the current study findings, the low-educated and low-income young males were the most high-risk population for drug overdose death in Iran. The essential role of education and job-creation policies to prevent addiction and opium-related death was clarified. Objectives Because of cultural, social, and geographical differences in Iranian drug abuser, the current study aimed to retrospective assessment of typical features of corpses due to opium intoxication including those on MMT in Isfahan, Iran, during a 6-year period. Patients and Methods 3. Data Collection The current epidemiological retrospective, cross sectional study was done during a 6-year period in Isfahan, Iran. Data Restrictions Corpses not being autopsied, unidentified bodies, and those without toxicological reports were excluded. Results A total of cases of opioid overdose death were recorded. Table 1. Demographic Characteristics of Bodies by Year. Year based on solar year P Age a Figure 1. References 1. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4. Leave a comment here:. Cookie Setting We use cookies to provide you with the best possible experience.

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