Heavy Drugs Research Articles

Is Urinary Beta-2 Microglobulin a Good Predictive Marker in Children With Pyelonephritis?

Copyright © 2013, Pediatric Infections Research Center This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Dear Editor, Regarding recently published article on urinary beta-2 microglobulin (s2MG) as a prognostic marker in children with pyelonephritis, some issues should be considered (1). s2MG is a small globular peptide with a molecular weight of 11800 Dalton which can be found on the surface of many cells. It consists of 100 amino acids with a disulfide-linked loop between amino acid 25 and 81; and its tertiary structure is homologous to the CH3IgG domain. s2MG passes freely through the glomerular membrane. Thereafter it is reabsorbed to an amount of maximum 99.9% by the proximal tubules (2). In aforementioned interesting article, the relation between urinary s2M to Creatinine ratio and its effect on kidney damage may not be an incidental finding. Although it is possible to apply s2M as a prognostic factor in patients with pyelonephritis, but exclusion criteria for patients should be extended more than mentioned. Other contributing factors in increased s2M are infections (such as CMV and HIV), malignancies (i.e. multiple myeloma), exposure to heavy metals (Mercury, Cadmium), kidney transplant, amyloidosis and drugs (such as Lithium, Cyclosporine, Cisplatin, Aminoglycosides). These issues should be taken into account and are considered in the exclusion criteria (3-6).

Stereo‐ and Regioselective Direct Multi‐Deuterium‐Labeling Methods for Sugars

Deuterium-labeled sugars can be utilized as powerful tools for the architectural analyses of high-sugar-containing molecules represented by the nucleic acids and glycoproteins, and chiral building blocks for the syntheses of new drug candidates (heavy drugs) due to their potential characteristics, such as simplifying the (1)H NMR spectra and the stability of C-D bonds compared with C-H bonds. We have established a direct and efficient synthetic method of deuterated sugars from non-labeled sugars by using the heterogeneous Ru/C-catalyzed H-D exchange reaction in D(2)O under a hydrogen atmosphere with perfect chemo- and stereoselectivities. The direct H-D exchange reaction can selectively proceed on carbons adjacent to the free hydroxyl groups, and the deuterium labeling of various pyranosides (such as glucose and disaccharides), as well as furanosides, represented by ribose and deoxyribose was realized. Furthermore, the desired number of deuterium atoms can be freely incorporated into selected positions by the site-selective protection of the hydroxyl groups using acetal-type protective groups because the deuterium exchange reaction never proceeds on positions adjacent to the protected hydroxyl groups.

Nodding Syndrome in Ugandan Children and Adolescents: Menage A Trios of Epilepsy, Autism, and Pediatric Catatonia

An enigmatic encephalopathy, coined “Nodding Syndrome” (NS) that is characterized by head nods, cognitive and motor impairments, eventual development of other seizures types and stunted growth, is afflicting youth and young adults in Northern Uganda in epidemic proportions [1-3]. The districts of Kitgum, Pader, and Lamwo are particularly affected. The etiology, prevention, and management of NS are mired in mystery despite scrutiny of international health organizations. During the last two years, detections of NS have dramatically increased with about 5,000 cases identified in the villages of the Pader district where more than 300 children have died due to the condition. These are probably underestimates as the number of detections keeps rising, also in neighboring districts. Children afflicted, usually between the ages of five and fifteen years, start to have nodding movements of the head that may be precipitated by sight or taste of food or presence of cold weather. Eventually the children develop cognitive, motor, and behavioral disabilities with ensuing malnutrition and growth retardation. Often there is rapid deterioration leading to an extremely high mortality rate due to malnutrition, opportunistic infections, accidents, or self-injury. Some believe that the disease started in 2003 when most of the Northern Ugandan population had moved to Internally Displaced People’s camps, predominantly affecting children and adolescents. The condition was first called a progressive cerebral-muscular-skeletal epileptogenic syndrome. Links with onchocerciasis and the associated river blindness epilepsy syndrome, cysticercosis, toxoplasmosis, schistosomiasis, trypanosomiasis, congenital syphilis, metabolic and nutritional disorders, intoxicants (heavy metals, poisons, and drugs), war zone exploded munitions and military ordinance materials contamination, endocrine anomalies, neoplasia, and autoimmune disorders have been investigated but remain unsubstantiated.

Big interest in heavy drugs

Big interest in heavy drugs

Continuing Medical Education (CME) credits

Substance use is highly prevalent among transgender (trans*) females and has been associated with negative health outcomes, including HIV infection. Little is known about psychosocial risk factors that may influence the onset of substance use among trans*female youth, which can contribute to health disparities during adulthood.We conducted a secondary data analysis of a study on HIV risk and resilience among trans*female youth (N = 292). Prevalence of substance use was assessed and multivariable logistic regression models were used to examine the relationship between posttraumatic stress disorder (PTSD), psychological distress, gender-related discrimination, parental drug or alcohol problems (PDAP) and multiple substance use outcomes.Most (69%) of the trans*female youth reported recent drug use. In multivariable analyses, those with PTSD had increased odds of drug use [AOR = 1.94 (95% CI = 1.09–3.44)]. Those who experienced gender-related discrimination had increased odds of drug use [AOR = 2.28 (95% CI = 1.17–4.44)], drug use concurrent with sex [AOR = 2.35 (95% CI = 1.11–4.98)] and use of multiple drugs [AOR = 3.24 (95% CI = 1.52–6.88)]. Those with psychological distress had increased odds of using multiple heavy drugs [AOR = 2.27 (95% CI = 1.01–5.12)]. Those with PDAP had increased odds of drugs use [AOR = 2.62 (95% CI = 1.43–4.82)], drug use concurrent with sex [AOR = 2.01 (95% CI, 1.15–3.51)] and use of multiple drugs [AOR = 2.10 (95% CI = 1.22–3.62)].Substance use is highly prevalent among trans*female youth and was significantly associated with psychosocial risk factors. In order to effectively address substance use among trans*female youth, efforts must address coping related to gender-based discrimination and trauma. Furthermore, structural level interventions aiming to reduce stigma and gender-identity discrimination might also be effective.

LIVING RELATED LIVER TRANSPLANTATION. IN WHICH CASES THIS OPTION HAS BEEN DISCARDED IN A PEDIATRIC LIVER TRANSPLANT PROGRAM IN CHILE?

P713 The technique of Living Related Living Transplantation (LRLT) opened new possibilities for planning transplantation in better conditions for children with emergency situations and chronic liver diseases. In Chile our program was started in 1993, incorporating the technique of LRLT in 1999. Since then, we have performed 17 LRLT in one of the centers belonging to our program, representing a 29, 8%. Actuarial survival in this series is 82, 4% and 74, 1% at 1 and 5 years. During that period more patients could have taken advantage of this innovative technique. For different reasons not all patients in whom LRLT was planned could be transplanted. The aim of this presentation is to analyze the reasons why LRLT was discarded as a therapeutic option. Material and Methods: All pediatrics patients belonging to one of the centers of our program were prospectively included in our Excel database that was reviewed for obtaining information about causes why the LRLT could not be done. Results: During that period LRLT was proposed in 28 cases, LRLT was performed in 17 of them (60, 7%). In 11 cases (39, 3%) this technique could not be used. The reasons for LRLT rejection were parent’s fear to surgical complications in 4 cases (3 fathers and 1 mother), 2 fathers with history of heavy drugs abuse, one mother because she was the only family support, 2 for medical reasons (1 father with fatty liver and one mother with breastfeeding) and only one father discarded for surgical technical reasons (two tiny left arteries). From these eleven cases the indications for liver transplant were acute liver failure (ALF) in 6, biliary atresia in 3 and miscellaneous in 2 cases. Nine were transplanted with cadaveric organs, but two of the patients with ALF died on the waiting list. Conclusions: LRLT is an excellent therapeutic option for acute and chronic terminal liver diseases. Different reasons impede that this therapeutic option could finally be performed. Among them, the most important is parent’s fear to surgery. Technical surgical reasons represent less than 10% of the total. Although most of the patients could finally be transplanted, mortality on waiting list was 33, 3% for patients with ALF. Efforts should be made to clarify any doubts about advantages and disadvantages of lrlt in each single case, allowing parent to take a free, well informed decision.

Identification of the aromatase inhibitor aminoglutethimide in urine by gas chromatography/mass spectrometry.

Aminoglutethimide is used therapeutically as an aromatase inhibitor in the treatment of metastatic breast cancer in post-menopausal women. For doping purposes, aminoglutethimide may be used for treatment of adverse effects of an extensive abuse of anabolic androgenic steroids (gynaecomastia) and to increase the testosterone concentration and stimulation of testosterone biosynthesis. The use of aromatase inhibitors has been prohibited for male athletes since September 1, 2001. The purpose of this study was to develop methods for the identification of the parent compound or its main metabolite and the inclusion of this information into established screening procedures in doping analysis. An excretion study was conducted using oral application of one single therapeutic dose (500 mg) of Orimeten. The analysis was performed by gas chromatography/mass spectrometry (GC/MS). Aminoglutethimide is excreted almost totally as unconjugated parent compound and is detectable by different screening procedures for up to 165 h. Most suitable for the detection of aminoglutethimide is the screening procedure for heavy volatile nitrogen-containing drugs ('Screening 2'). However, since only competition samples are analysed in that screening procedure, the additional inclusion of aminoglutethimide in the screening procedure for anabolic androgenic agents ('Screening 4') is recommended. Full mass spectra and diagnostic ions for the analysis of aminoglutethimide are presented.

Structure of the ArsA ATPase: the catalytic subunit of a heavy metal resistance pump.

Active extrusion is a common mechanism underlying detoxification of heavy metals, drugs and antibiotics in bacteria, protozoa and mammals. In Escherichia coli, the ArsAB pump provides resistance to arsenite and antimonite. This pump consists of a soluble ATPase (ArsA) and a membrane channel (ArsB). ArsA contains two nucleotide-binding sites (NBSs) and a binding site for arsenic or antimony. Binding of metalloids stimulates ATPase activity. The crystal structure of ArsA reveals that both NBSs and the metal-binding site are located at the interface between two homologous domains. A short stretch of residues connecting the metal-binding site to the NBSs provides a signal transduction pathway that conveys information on metal occupancy to the ATP hydrolysis sites. Based on these structural features, we propose that the metal-binding site is involved directly in the process of vectorial translocation of arsenite or antimonite across the membrane. The relative positions of the NBS and the inferred mechanism of allosteric activation of ArsA provide a useful model for the interaction of the catalytic domains in other transport ATPases.

Anorexia nervosa and bulimia nervosa in alcohol-dependent men and women and their relatives.

Many of the studies linking anorexia nervosa and bulimia nervosa to substance use disorders suffer from problems with small samples; some lack rigorous definitions of the syndromes, and it is difficult to determine whether eating problems were primarily temporary consequences of heavy substance use or drugs were temporarily used in an effort to control appetite. The goal of this study was to evaluate the relationship between alcohol dependence and eating disorders. Structured interviews were carried out with 2,283 women and 1,982 men as part of the Collaborative Study on the Genetics of Alcoholism. Data on drug abuse and dependence, psychiatric disorders, and symptoms of anorexia and bulimia were evaluated among alcohol-dependent probands, their relatives, comparison probands, and their relatives. Lifetime rates for anorexia and bulimia were 1.41% and 6.17%, respectively, for the alcohol-dependent women, and bulimia was observed in 1.35% of the alcoholic men. However, once the impact of additional primary diagnoses was controlled for, anorexia was seen in only 1.26% of the women with primary alcohol dependence and none of the alcohol-dependent men; the rates for bulimia were 3.46% and 0.72%, respectively. There was no evidence of a strong familial crossover between alcohol dependence and anorexia or bulimia. While the rate of anorexia was not elevated in alcoholics after controlling for other disorders, bulimia did occur at a greater than expected rate. However, both eating disorders were relatively rare, and much of the association with alcoholism occurred in the context of additional preexisting or secondary psychiatric disorders.

Determination of lead in illicit drugs by electrothermal atomic absorption spectrometry using palladium as chemical modifier

A method for the determination of lead in illicit heavy drugs by electrothermal atomic absorption spectrometry using palladium as a chemical modifier was developed. A sample of drug, 0.5 g, was dissolved in 2 ml of HNO 3 35.0% (v/v), diluting to 10 ml with ultrapure water. First, a comparative study of palladium, magnesium and palladium-magnesium used as chemical modifiers was carried out, and it was found that palladium alone is adequate to stabilize lead at a charring temperature of 1000 ° C. The optimum atomization temperature was 2400 ° C. A study on the insertion of a cool-down step before the atomization step and a study on the omission of the charring step were made. Neither approach was advantageous. A limit of detection of 31.4 μg kg −1 and a characteristic mass of 24.4 pg were obtained, with analytical recoveries between 98.0 and 105.0% for a 2.5–40 μg l −1 concentration range. The within-batch precision ( n = 11) was oscillated between 6.4 and 0.2% for a drug solution spiked with 0 and 40 μg l −1, respectively. Finally, a study of some interferences, and a study of the precision and analytical recovery on the amount of sample were also carried out.

Individualized drug utilization statistics. Analysing a population's drug use from the perspective of individual users.

The Danish retail pharmacies' drug subsidy system is completely computerized. The data are person-identifiable, making it possible to chart the population's drug use from the perspective of individual users. We decided to explore the potential of this data source and to analyse heavy drug users specifically. The analysis encompassed all 890,352 prescriptions presented by citizens of Odense in 1991. There was a total sales volume of 32 million defined daily doses consumed by 113,468 adult drug users, corresponding to 65.1% of the adult population. We found 2388 heavy drug users, defined by an annual purchase of more than 2000 defined daily doses. Heavy drug users accounted for 1.4% of the adult population and 22.9% of drug sales. They were remarkably well characterized by their main therapeutic class, which constituted a median of 47% of their drug use. A median of 97% of each heavy user's drugs were issued by one main prescriber. We conclude that heavy drug use can generally be ascribed to severe disease rather than to irresponsible prescribing. For the most important drug classes, we present various epidemiological measures of drug use, including 1-year prevalence, incidence, duration of therapy and some measures of skewness in utilization. If analysed regularly these measures can disclose subtle trends in clinical drug use that would not be evident from the wholesale figures.

Mixed use of psychiatric drugs and alcohol by Finnish university students participating in a health screening.

To obtain descriptive data on the mixed use of psychiatric drugs and alcohol. The difference and associations of health and mental risk factors between mixed users and others were also studied. A self-administered questionnaire as part of a general health screening. First-year university students enrolled in the Finnish Student Health Service in Helsinki. Foreign students and those aged 30 years or over were excluded. 3,836 students were invited. The participation rate was 73.2% for the female and 53.2% for the male students. The mixed use of psychiatric drugs and alcohol with the aim of getting high, at least once, was reported by 3.6% of the female and 3.1% of the male students. However, only 1.0% had tried this mixed use more than once. Mixed users were more often smokers, heavy drinkers, or users of cannabis or heavy drugs. Male students tended to be mixed users because of anxiety, low self-esteem, and fears. Depression, stress, and sensation seeking were associated with mixed use in female students. Mixed use of psychiatric drugs and alcohol by young Finnish university students is still rare. There is a strong accumulation of other addictive behaviours among mixed users. Extra-personal reasons for mixed use were more prevalent among female students, and intra-personal reasons among male students.

Current knowledge on potential health benefits of Spirulina

Spirulina is a microscopic filamentous alga that is rich in proteins, vitamins, essential amino acids, minerals and essential fatty acids like γ-linolenic acid (GLA). It is produced commercially and sold as a food supplement in health food stores around the world. Up to very recently, the interest in Spirulina was mainly in its nutritive value. Currently, however, numerous people are looking into the possible therapeutic effects of Spirulina. Many pre-clinical studies and a few clinical studies suggest several therapeutic effects ranging from reduction of cholesterol and cancer to enhancing the immune system, increasing intestinal lactobacilli, reducing nephrotoxicity by heavy metals and drugs and radiation protection. This paper presents a critical review of some published and unpublished data on therapeutic effects of Spirulina.

IUD use and endometrial bleeding

Bleeding disturbances account for 41-52% of all IUD discontinuations. These bleeding disturbances include an increase in menstrual blood loss (MBL) intermenstrual bleedings (IMBs) and prolonged duration of menstruation. IUD users experience an increase of MBL of 50-75% which continues throughout the duration of IUD use. MBL decreases after insertion of a progestin-releasing IUD. A progestin-releasing IUD can treat women suffering from excessive bleeding during menstruation. MBL of at least 60-80 ml causes iron deficiency and anemia. Since due to infections and malnutrition iron balance is especially important in women from developing countries copper T IUD use threatens their health. IMBs are most frequent during the first months following IUD insertion. IMBs differ with the IUD type. IMB generally results in minimal blood loss (4-5 ml) which has no negative health effects in IUD users. IUD-induced IMB may keep many women from using the IUD in cultures where irregular bleeding is unacceptable. The copper T IUD prolongs menstruation by about 1 day while the progestogen-releasing IUD prolongs it by about 2 days. Prolongation of menses rarely contributes to discontinuation. Ways to manage bleeding disturbances other than removal include counseling before insertion and when disturbances occur; in cases of heavy blood losses antifibrinolytic agents nonsteroidal anti-inflammatory drugs and iron supplementation; and in cases of IMB changing either the IUD or its location. The most important way to minimize the consequences of IUD-related bleeding problems and increase IUD acceptability is good counseling from professionals with experience confidence and adequate knowledge of the effect of the IUD on bleeding patterns.

Drug abuse in patients visiting a psychiatric emergency unit

Among 1016 patients visiting the emergency psychiatric clinic at Danderyd Hospital, 40 (4%) were diagnosed as being drug abusers. When the medical records for these patients were later examined individually, it was found that simultaneously with the rated drug abuse 25 of these 40 patients were also heavy alcohol and/or narcotic drugs abusers; only 15 were “pure” abusers of benzodiazepines and the assumed etiologies were different, ranging from a start with acute stress situation, panic disorder, severe obsession to suspected psychoses. The methodological problem in analysing these data is discussed.

Chemistry and molecular biology of platinum anticancer drugs

Abstract

Membranous nephropathy: an overview.

Membranous nephropathy (MN) accounts for about 20 percent of cases of the nephrotic syndrome. The importance of renal biopsy in establishing the diagnosis is emphasized. In the great majority of MN patients, no etiologic factor can be discerned. In a significant minority, MN appears to be a manifestation of sarcoidosis, diabetes, lupus, syphilis, malaria, or toxicity from heavy metals or drugs. In some cases the "cause" is neoplasia (including lymphoma) or a viral infection. Massive proteinuria, hypoproteinemia and edema are the principal manifestations of MN, finally resulting in renal failure. Treatment consists chiefly of diet and diuretic drugs. In the more pronounced cases, corticosteroids may have a favorable effect and in very resistant cases, cyclophosphamide is indicated. Judicious use of these modalities if often associated with the diminution or disappearance of the clinical signs of MN.

Superprecipitation of actomyosin extracted from crayfish skeletal muscle: the effect of heavy metal cations, EDTA and drugs.

AbstractActomyosin from crayfish skeletal muscle will superprecipitate in the presence of ATP without added Ca++ or Mg++. EDTA totally inhibits Ca++‐induced superprecipitation of actomyosin, but in some cases Mg++ will reverse this effect. It is suggested that Mg++ and not Ca++ is a prerequisite for superprecipitation with ATP alone. EDTA only partly inhibits heavy metal‐induced actomyosin superprecipitation.Heavy metal cations induce far greater actomyosin superprecipitation than Ca++, and they can even enhance previously formed Ca++‐induced precipitates. It is suggested that heavy metal cations may be more strongly bound to crayfish actomyosin than Ca++, and that they may displace Ca++ from existing actomyosin binding sites. Heavy metal potentiation of muscular contraction may thus involve direct action at myofibril binding sites.Caffeine and quinine are without effect either on the rate or extent of development of actomyosin precipitates in the presence of ATP, ATP plus Ca++, and ATP plus Zn++. These observations rule out any direct effect of these drugs at the myofibril level during drug‐induced potentiation of muscular contraction.

Syndrome of Peutz (melanoplakia and small intestinal polyposis): observations with special reference to the oral pigmentation.

MELANOPLAKIA—a brown-black oral mucosal pigmentation—is literally a black plate, and by definition the pigment need not be melanin. It has been described under various terms but most probably is a lentigo. Although opinions differ, the red free margins of the lips are herein considered as mucous—rather than cutaneous—surfaces. Melanoplakia is physiologic in Negroes, frequent in yellow and brown races, and relatively frequent in white persons with dark complexion. It also has been associated with (1) local factors—including heavy metals, foods, dental abnormalities, foreign bodies, dyes, acids, gases, and drugs; (2) radiant energy, especially in the ultraviolet range; (3) malignant growths, including Hutchinson's lentigo maligna—7% of malignant melanomas arise from an initial lesion in the oral mucosa; (4) systemic diseases—including Addison's disease, cachexia, carcinomatosis, diabetes, hemochromatosis, hyperthyroidism, tuberculosis, malaria, Niemann-Pick disease, hepatic diseases, pancreatic diseases, gynecologic diseases, and rarely pernicious anemia, pellagra, sprue, and Gaucher's disease, and (5)