Correlation between Resistin,Tuberculosis and Khat Addiction: A Study from South Western Province of Saudi Arabia

Tuberculosis(TB) is a disease of global significance, which accounts for a death in every 15 seconds. Recent studies shows TB is rising in certain parts of the world, and Saudi Arabia is one of them. Several factor contribute in predisposing the subjects for infection including but not limited to addiction to various compounds which have immune modulation properties, such as amphetamines and Heroin etc. Khat a plant whose leaves are chewed for its euphoric effect in east Africa and Arabian Peninsula including Saudi Arabia, is considered as mildly addictive, and its principle compound, Cathinone shares structural and functional similarity with amphetamine a known immunomodulator. Tuberculosis being a disease of immune modulation has a varied spectrum of complex interplay of proinflammatory molecules, resistin is one of them. In the present study, we try to explore the trinity of khat addiction, serum resistin level and tuberculosis by correlating the serum resistin level in non khat addicted healthy subjects, khat addicted healthy subjects, and in patients, both khat addicted and non khat addicted, with active tuberculosis. We observed significantly higher resistin level among the apparently healthy khat addicted subjects as compared to non addicted healthy controls. Thereafter, when we compare the resistin levels between khat addicted and non khat addicted TB patients we did not found significant difference between the two groups. However bacillary load was observe to be significantly higher among the khat addicted TB patient as compare to non addicted one. Validation of above results in animal model revealed dose dependant increase in bacillary growth in the Wistar rats treated with khat. Taken together these results suggest the role of khat in immune modulation albeit in the limited frame of resistin level.     

MicroRNAs regulate synaptic plasticity underlying drug addiction

Chronic use of drugs of abuse results in neurochemical, morphological and behavioral plasticity that underlies the emergence of compulsive drug seeking and vulnerability to relapse during periods of attempted abstinence. Identifying and reversing addiction‐relevant plasticity is seen as a potential point of pharmacotherapeutic intervention in drug‐addicted individuals. Despite considerable advances in our understanding of the actions of drugs of abuse in the brain, this information has thus far yielded few novel treatment options addicted individuals. MicroRNAs are small noncoding RNAs that can each regulate the translation of hundreds to thousands of messenger RNAs. The highly pleiotropic nature of miRNAs has focused attention on their contribution to addiction‐relevant structural and functional plasticity in the brain and their potential utility as targets for medications development. In this review, we discuss the roles of miRNAs in synaptic plasticity underlying the development of addiction and then briefly discuss the possibility of using circulating miRNA as biomarkers for addiction.     

Pathways and Networks-Based Analysis of Candidate Genes Associated with Nicotine Addiction

Nicotine is the addictive substance in tobacco and it has a broad impact on both the central and peripheral nervous systems. Over the past decades, an increasing number of genes potentially involved in nicotine addiction have been identified by different technical approaches. However, the molecular mechanisms underlying nicotine addiction remain largely unclear. Under such situation, a comprehensive analysis focusing on the overall functional characteristics of these genes, as well as how they interact with each other will provide us valuable information to understand nicotine addiction. In this study, we presented a systematic analysis on nicotine addiction-related genes to identify the major underlying biological themes. Functional analysis revealed that biological processes and biochemical pathways related to neurodevelopment, immune system and metabolism were significantly enriched in the nicotine addiction-related genes. By extracting the nicotine addiction-specific subnetwork, a number of novel genes associated with addiction were identified. Moreover, we constructed a schematic molecular network for nicotine addiction via integrating the pathways and network, providing an intuitional view to understand the development of nicotine addiction. Pathway and network analysis indicated that the biological processes related to nicotine addiction were complex. Results from our work may have important implications for understanding the molecular mechanism underlying nicotine addiction.     

Class-Based Chronicities of Suffering and Seeking Help: Comparing Addiction Treatment Programs in Uganda

Based on ethnographic fieldwork, this article looks at changing discourses and practices in the field of mental health care in Uganda. In particular, it analyzes two psychotherapeutic institutions designed to treat drug- and alcohol-addiction, and their accessibility and affordability for people from different class backgrounds. The first center is a high-class residential facility near Kampala which offers state-of-the-art addiction therapy, but is affordable only for the rich. The second center, a church-funded organization in Northern Uganda, cares mainly for people from poor, rural families who cannot afford exp/tensive treatment. Comparing the two centers provides important insights not only into the temporalities of mental illness, substance abuse and mental health care, but also into broader socio-economic dynamics and understandings of suffering in contemporary Uganda. The term ‘class-based chronicities’ refers to the way both the urgency with which people seek treatment (when has someone suffered enough?) and the length of treatment they receive (when is someone considered ‘recovered’?) are highly class-dependent. On a theoretical level, the article shows how psychotherapeutic models operate as philosophical systems which not only impact on treatment practices, but also produce different addiction entities and addiction-related subjectivities. As such, it contributes to an emerging anthropology of addiction.     

毒品成瘾与脑组织基因表达谱的研究进展

毒品成瘾是由滥用毒品外在因素与遗传易感性等内在因素共同作用而导致的一种慢性脑疾病; 毒品成瘾的机制目前还不十分清楚。毒品成瘾研究的一个主要目标是鉴别和分离毒品导致脑功能障碍的分子机制; 采用高通量的基因表达谱技术研究毒品成瘾者在不同状态下脑基因表达全貌, 对深入认识毒品成瘾的机制具有重要的意义。文章综述了毒品成瘾的遗传机制及高通量脑组织基因组表达技术——SAGE和微阵列(Microarry)在毒品成瘾研究中的进展。     

Precursor or sequela: pathological disorders in people with Internet addiction disorder

Background

This study aimed to evaluate the roles of pathological disorders in Internet addiction disorder and identify the pathological problems in IAD, as well as explore the mental status of Internet addicts prior to addiction, including the pathological traits that may trigger Internet addiction disorder.

Methods and Findings

59 students were measured by Symptom CheckList-90 before and after they became addicted to the Internet. A comparison of collected data from Symptom Checklist-90 before Internet addiction and the data collected after Internet addiction illustrated the roles of pathological disorders among people with Internet addiction disorder. The obsessive-compulsive dimension was found abnormal before they became addicted to the Internet. After their addiction, significantly higher scores were observed for dimensions on depression, anxiety, hostility, interpersonal sensitivity, and psychoticism, suggesting that these were outcomes of Internet addiction disorder. Dimensions on somatisation, paranoid ideation, and phobic anxiety did not change during the study period, signifying that these dimensions are not related to Internet addiction disorder.

Conclusions

We can not find a solid pathological predictor for Internet addiction disorder. Internet addiction disorder may bring some pathological problems to the addicts in some ways.     

Death Following Inhalation of Mercury Vapor at Home.

Confusion exists among physicians over the legal requirements and appropriate prescribing of narcotics to addicted or habitual users of narcotics. The result has often been either (1) the deprivation of appropriate treatment for patients who desire detoxification or adequate pain relief, or (2) illegal prescribing by physicians. Because most narcotics are potent and dangerous substances, certain legal restrictions are necessary to protect the general public. State-approved programs have been established to prescribe methadone and propoxyphene napsylate for addiction treatment. Current laws and regulations in California permit every practicing physician to provide effective and safe treatment for addiction and pain relief.     

Opium Addiction Increases Interleukin 1 Receptor Antagonist (IL-1Ra) in the Coronary Artery Disease Patients

Background

There is evidence that opium addiction has immunosuppressant effects. Coronary artery disease (CAD) is a condition resulted from atherosclerosis which is dependent on the immune response.

Purpose

To evaluate plasma levels of interleukin-6 and interleukin-1Ra in 30 patients with three-vessel coronary artery disease, ejection fraction of more than 35% and to evaluate their changes after prognostic treadmill test in 15 opium addicted and 15 non-addicted patients.

Methods

The participants underwent prognostic treadmill test and plasma levels of interleukin-6 (IL-6) and interleukin-1Ra (IL-1Ra) were evaluated with ELISA method before, just after and 4 hours after the test.

Results

IL-1Ra (2183 pg/ml) tended to decrease over time in the opium addicted group (1372 pg/ml after prognostic treadmill test and 1034 pg/ml 4 hours after that), although such decrease did not reach the statistical significance. IL-1Ra levels were significantly higher in opium addicted than in non addicted patients. Opium addiction had no significant effect on IL-6 changes.

Conclusion

Consumption of opium in CAD patients is associated with higher IL-1Ra levels.     

气味线索对小鼠形成吗啡依赖及渴求的影响

利用条件化位置偏好模型研究气味线索对吗啡依赖及渴求的影响,其结果发现,单一嗅觉条件刺激使小鼠建立条件化位置偏好,形成吗啡依赖。当改变外界环境,动物进入完全新异的环境后依然寻求与吗啡相关的气味线索,说明吗啡相关气味条件线索诱发了小鼠对吗啡的渴求。多巴胺D1或D2受体拮抗剂能阻断小鼠对气味线索的寻求。该结果表明嗅觉系统在药物成瘾过程中具有一定作用。     

Not You: Addiction,Relapse, and Release in Uganda

In recent years, alcohol abuse and dependence have become topics of increasing concern in Uganda, but the chronic relapsing brain disease model of addiction remains only one of many ways of understanding and addressing alcohol-related problems there. For many Ugandan Pentecostals and spirit mediums to be addicted is to be under the control of a being that comes from outside the self. Where these two groups differ, and here they differ strongly, is in regard to the moral valence of these external spirits and what ought to be done about them. This article draws on four years of collaborative ethnographic fieldwork to explore the affordances of these ways of viewing and experiencing addiction and recovery for Ugandans attempting to leave alcohol behind. While the idioms of bondage, dedication, and possession are at times severe, this article argues that they contain within them concepts and practices that point away from models of addiction as a chronic relapsing brain disease and towards the possibility of release.

     

Micronucleus formation and DNA damage in buccal epithelial cells of Indian street boys addicted to gasp 'Golden glue'

Genotoxicity of glue sniffing/huffing and tobacco use has been examined in 302 street boys (median age 13 years) and 50 age-matched control school boys who were neither tobacco nor glue users. All the street boys were tobacco users. In addition, 155 were addicted to gasp an industrial adhesive popularly known as 'Golden glue'. Micronucleus (MN) frequency was determined as a measure of chromosomal breakage in exfoliated buccal epithelial cells (BECs) and DNA double strand breaks were quantitatively assessed by counting γ-H2AX foci using immunofluorescence microscopy. Micronucleated cell frequencies (MCFs) in BEC of glue non-addicted (only tobacco) and addicted (tobacco plus glue) street boys were 1.87 ± 1.06‰ and 4.04 ± 2.55‰ respectively, which were significantly higher than that of control (0.32 ± 0.11‰, p<0.0001). Similarly, the numbers γ-H2AX foci in nuclei of BEC were 2.3- and 5.2-times more than control in glue non-addicted and addicted street boys respectively (p<0.0001). Spearman's rank correlation revealed a strong positive association between years of glue addiction with MCFs and γ-H2AX foci numbers, and the association between glue addiction and chromosomal and DNA damage remained positive and significant after controlling income, spending on addiction and loss of appetite as potential confounders in multivariate logistic regression analysis. Thus, addiction to tobacco among the street children in India is associated with chromosomal and DNA damage in BECs and the severity of these changes is significantly increased by the habit of sniffing/huffing of industrial glue.     

Female Narcotic Addicts: A Follow-up Study of Criminal and Addiction Careers

A sample of 66 female narcotic addicts first examined in prison in 1967-8 was followed-up four years later. At the end of the period of follow-up 36% were off narcotics, 32% were still addicted, and 15% had died. Altogether 62% committed further offences. Drug offences and offences against property were almost equally frequent and accounted for over two-thirds of all convictions. There was no evidence of a link between prostitution and narcotic addiction. A significant association was found between continued delinquency and continued addiction during the period of follow-up. Addiction career and criminal career coincided in over three-quarters of the subjects, who tended either to continue manifesting both forms of deviant behaviour (46%) or to relinquish both (30%). The findings are in keeping with the view that narcotic addiction and crime are not causally related but may be parallel effects of common underlying factors leading to social deviance.     

Systems biology modeling reveals a possible mechanism of the tumor cell death upon oncogene inactivation in EGFR addicted cancers

Despite many evidences supporting the concept of "oncogene addiction" and many hypotheses rationalizing it, there is still a lack of detailed understanding to the precise molecular mechanism underlying oncogene addiction. In this account, we developed a mathematic model of epidermal growth factor receptor (EGFR) associated signaling network, which involves EGFR-driving proliferation/pro-survival signaling pathways Ras/extracellular-signal-regulated kinase (ERK) and phosphoinositol-3 kinase (PI3K)/AKT, and pro-apoptotic signaling pathway apoptosis signal-regulating kinase 1 (ASK1)/p38. In the setting of sustained EGFR activation, the simulation results show a persistent high level of proliferation/pro-survival effectors phospho-ERK and phospho-AKT, and a basal level of pro-apoptotic effector phospho-p38. The potential of p38 activation (apoptotic potential) due to the elevated level of reactive oxygen species (ROS) is largely suppressed by the negative crosstalk between PI3K/AKT and ASK1/p38 pathways. Upon acute EGFR inactivation, the survival signals decay rapidly, followed by a fast increase of the apoptotic signal due to the release of apoptotic potential. Overall, our systems biology modeling together with experimental validations reveals that inhibition of survival signals and concomitant release of apoptotic potential jointly contribute to the tumor cell death following the inhibition of addicted oncogene in EGFR addicted cancers.     

Cytokine storm intervention in the early stages of COVID-19 pneumonia

Clinical intervention in patients with corona virus disease 2019 (COVID-19) has demonstrated a strong upregulation of cytokine production in patients who are critically ill with SARS-CoV2-induced pneumonia. In a retrospective study of 41 patients with COVID-19, most patients with SARS-CoV-2 infection developed mild symptoms, whereas some patients later developed aggravated disease symptoms, and eventually passed away because of multiple organ dysfunction syndrome (MODS), as a consequence of a severe cytokine storm. Guidelines for the diagnosis and treatment of SARS-CoV-2 infected pneumonia were first published January 30^th, 2020; these guidelines recommended for the first time that cytokine monitoring should be applied in severely ill patients to reduce pneumonia related mortality. The cytokine storm observed in COVID-19 illness is also an important component of mortality in other viral diseases, including SARS, MERS and influenza. In view of the severe morbidity and mortality of COVID-19 pneumonia, we review the current understanding of treatment of human coronavirus infections from the perspective of a dysregulated cytokine and immune response.     

Appropriation and Dementia in India

Biomedical technologies like MRI scans offer a way for carers and people with dementia to ‘see’ pathology, as a means to reorient their perceptions of the body and functionality. Through interpretive and syncretic processes, the MRI and the diagnosis of dementia facilitate the incorporation of the clinical category ‘dementia’ into social understandings of illness and care in India. Complex shifts occur as families and providers move from socio-cultural explanations of disruption to bio-social etiologies of the disease ‘dementia’ and then to socio-ecological frameworks of causality. Both the biomedicalisation of illness and the localisation of illness occur as the clinical category ‘dementia’ is folded into local understandings of illness and care. Through elucidating how the dialectic between biomedical and local knowledge is operationalized, we offer insights into how dementia is absorbed and appropriated into Indian cultural contexts.     

Caida de Mollera among Children of Mexican Migrant Workers: Implications for the Study of Folk Illnesses

Information about the folk illness caida de mollera was collected from Mexican and Mexican American migrant mothers who had treated their children for the illness, and from physicians in a clinic that served this population. These physicians believed that the vast majority of the sets of symptoms were worthy of medical attention and could be life threatening if not treated. This research report concurs with other studies that suggest that although Mexican folk illnesses are conceptualized to have folk-social and psychological causes, they are also seen to have biological causes and physiological symptoms that can be treated by biomedical methods. This report outlines a model for understanding aspects of folk illnesses that includes folk vs. biomedical ideas about disease, causes vs. symptoms, and psychological vs. physiological aspects of sickness. It also suggests that the kinds of questions anthropologists ask about these illnesses may need to be modified—shifting away from questions about treatments of causes and refocusing on those about the treatment of physiological symptoms—if we are to more fully understand home approaches to the management of these illnesses, [folk illnesses, Mexican, Mexican American, farmworkers]     

The genetics of the opioid system and specific drug addictions

Addiction to drugs is a chronic, relapsing brain disease that has major medical, social, and economic complications. It has been established that genetic factors contribute to the vulnerability to develop drug addiction and to the effectiveness of its treatment. Identification of these factors may increase our understanding of the disorders, help in the development of new treatments and advance personalized medicine. In this review, we will describe the genetics of the major genes of the opioid system (opioid receptors and their endogenous ligands) in connection to addiction to opioids, cocaine, alcohol and methamphetamines. Particular emphasis is given to association and functional studies of specific variants. We will provide information on the sample populations and the size of each study, as well as a list of the variants implicated in association with addiction-related phenotypes, and with the effectiveness of pharmacotherapy for addiction.     

Changes in succinic dehydrogenase activity in the central nervous system of mice during morphine dependence development, withdrawal and naloxone treatment

The possible role of succinic dehydrogenase (SD) in producing physical dependence to morphine by affecting tissue respiration was investigated in Swiss albino mice during the development of morphine tolerance through a period of addiction and naloxone withdrawal therapy. Tolerance and physical dependence were induced by injecting the mice with morphine sulfate subcutaneously at 8-hour intervals, increasing the dose from 10 mg/kg BW every 24 h for 15 days. The animals were considered to be addicted when they were able to tolerate an otherwise lethal dose of 150 mg/kg 3 times a day. Results indicated that succinic dehydrogenase was inhibited throughout the 15-day period of morphine administration and that this effect was greatest in tolerant animals. Increasing the dose and duration of treatment did not cause further decreases in enzyme activity; instead, after 15 days levels of enzyme activity increased in addicted animals compared with tolerant mice. Furthermore, morphine abstinence for 2 days, markedly increased the levels of SD activity, while 6 days of abstinence had little effect. Naloxone withdrawal at each stage was associated with increased SD activity, but the increase was significant only in tolerant mice.