ABSTRACT
The chemsex or slamsex phenomenon has attracted attention worldwide, with concerns also expressed by health professionals for the spread of sexually transmitted diseases. Mephedrone or 4-methylmethcathinone, a substituted cathinone homolog of ephedrine, is one of the most popular substances used as a cheaper alternative to other traditional drugs. Fatal cases of chemsex are still rare. We present here the first case-report to the best of our knowledge of a mephedrone-related acute toxicity case in Parma (Italy) detected and quantitated in biological specimens (2.0â¯mg/L in urine sample, 1.1â¯mg/L in bile and 1.0â¯mg/L in central blood while 0.8â¯mg/L in peripheral blood). None of the other most common drugs of abuse could be detected. Autopsy findings such as facies edematosa, oedema and polyvisceral congestion, interstitial petechiae are compatible elements with a death from acute cardio-respiratory failure, with peri-mortem agony of few minutes in which the cardiac hypertrophy, the moderate aortocoronary sclerosis and mephedrone injection have played a substantial role in the evaluation of the final cause due to an accidental acute intoxication with mephedrone.
Subject(s)
Methamphetamine/analogs & derivatives , Autopsy , Fatal Outcome , Forensic Toxicology , Humans , Male , Methamphetamine/blood , Methamphetamine/poisoning , Methamphetamine/toxicity , Middle AgedABSTRACT
Heart failure is a complex syndrome characterized by the activation of hemodynamic, immunologic and neurohormonal systems, which have beneficial effects in the short run, but will ultimately lead to secondary end-organ damage with worsening of LV remodeling and subsequent cardiac decompensation. A very important role seems to be played by modifications of the pituitary hormone systems. Due to the neurohormonal activation there is an increase in the activity in the renin angiotensin system, in the adrenergic nervous system, and in the cytokine system. In heart failure there is a decrease in many anabolic hormones, such as a decrease of GH and IGF-I, of DHEA/DHEAS with normal or increased F, and a decrease of LH and sex steroids, resulting in an important catabolic drive, capable of contributing to the development of cardiac failure and to sarcopenia and/or cachexia, frequently observed in the advanced stages of the disease. However, these hormone alterations have been described in relatively young patients with chronic heart failure, since the mean age of all the subjects studied was of about 60 yr and none of the studies have specifically addressed this issue in the very old patients, who represent the largest portion of population affected by this pathological condition. The role of hormone replacement therapy needs to be verified in a population of elderly patients with heart failure.
Subject(s)
Cardiac Output, Low/physiopathology , Pituitary Gland/physiopathology , Aged , Chronic Disease , Hormones/metabolism , Humans , Pituitary Hormones/metabolismSubject(s)
Blood Pressure , Diet, Reducing , Insulin-Like Growth Factor I/metabolism , Obesity/diet therapy , Obesity/physiopathology , Weight Loss , Adult , Female , Hormones/blood , HumansABSTRACT
Aging is associated with a selective decline in circulating levels of dehydroepiandrosterone (DHEA) and its sulfate, with no major changes in cortisol secretion. In young subjects, serum levels of both DHEA and cortisol are regulated according to a circadian rhythm, and an age-related attenuation of DHEA, but not cortisol, circadian rhythmicity has been reported. Several trials have evaluated the effects of DHEA supplementation in elderly subjects, although the results are still controversial. However, no data are available on the 24-hour profile of DHEA circulating levels in elderly subjects with DHEA administration. In the present study, we evaluated the circadian rhythms of DHEA, cortisol, and the cortisol/DHEA molar ratio in old subjects treated with either placebo (old-PL) or a single 50-mg dose of DHEA (old-D), both administered orally at 0700 hours. For each variable, the circadian profiles were compared with those obtained in young control subjects. The group of young subjects displayed a circadian rhythm for both DHEA and cortisol serum concentrations but no rhythm for the cortisol/DHEA molar ratio. In the old-PL group, the circadian rhythm of DHEA was completely abolished, whereas significant rhythms for both cortisol and the cortisol/DHEA molar ratio were observed. Particularly, at each time point, the cortisol/DHEA molar ratio was significantly higher in these subjects versus the young group. In the old-D group, the circadian rhythm of DHEA was completely restored and was comparable to that observed in the young group. Analogous to the observations in young subjects, the profile of the cortisol/DHEA molar ratio in old-D subjects did not display any circadian rhythmicity, the values being almost completely comparable to those observed in young controls. Our data demonstrate that the circadian rhythm of DHEA is totally abolished in elderly subjects. A single 50-mg dose of DHEA administered orally at 0700 hours restores the circadian rhythmicity of serum DHEA and almost completely normalizes the 24-hour profile of the cortisol/DHEA molar ratio in old subjects without affecting the cortisol circadian rhythm.
Subject(s)
Aging/blood , Circadian Rhythm , Dehydroepiandrosterone/blood , Dehydroepiandrosterone/pharmacology , Hydrocortisone/blood , Administration, Oral , Adult , Aged , Female , Humans , Male , Osmolar ConcentrationSubject(s)
Aging/metabolism , Dehydroepiandrosterone/administration & dosage , Dehydroepiandrosterone/metabolism , Administration, Oral , Adult , Aged , Aged, 80 and over , Biological Availability , Dehydroepiandrosterone/pharmacokinetics , Dehydroepiandrosterone Sulfate/metabolism , Dehydroepiandrosterone Sulfate/pharmacokinetics , Estradiol/blood , Humans , Male , Steroids/metabolism , Testosterone/metabolism , Time FactorsSubject(s)
Blood Pressure , Insulin-Like Growth Factor I/analysis , Obesity/physiopathology , Body Constitution , Dehydroepiandrosterone Sulfate/blood , Female , Humans , Hypertension/blood , Hypertension/complications , Insulin-Like Growth Factor Binding Protein 1/blood , Insulin-Like Growth Factor Binding Protein 3/blood , Obesity/blood , Obesity/complications , Obesity/pathology , Reference ValuesSubject(s)
Heart Failure/complications , Heart Failure/drug therapy , Human Growth Hormone/deficiency , Human Growth Hormone/therapeutic use , Aged , Aged, 80 and over , Chronic Disease , Dose-Response Relationship, Drug , Heart Failure/physiopathology , Humans , Insulin-Like Growth Factor I/analysis , Male , Recombinant Proteins/therapeutic use , Stroke Volume/drug effects , Time FactorsSubject(s)
Body Composition/drug effects , Enzyme Inhibitors/therapeutic use , Finasteride/therapeutic use , Lipoproteins/blood , Oxidoreductases/antagonists & inhibitors , Prostatic Hyperplasia/drug therapy , Prostatic Hyperplasia/enzymology , Prostatic Hyperplasia/pathology , Aged , Cholestenone 5 alpha-Reductase , Dihydrotestosterone/blood , Humans , Male , Middle Aged , Prostatic Hyperplasia/bloodABSTRACT
Growth hormone (GH) secretion is decreased during aging in humans and in rodents. This decrease may be due to increased hypothalamic somatostatin release, which is inhibited by cholinergic agonists, or to decreased secretion of GHRH. Alpha-glyceryl-phosphorylcholine (alpha-GFC) is a putative acetylcholine precursor used in the treatment of cognitive disorders in the elderly. In order to learn what effect alpha-GFC had on GH secretion, GH-release hormone (GHRH) was given to young and old human volunteers, with or without the addition of alpha-GFC. GH secretion was greater in the younger subjects than in the old individuals, and both groups had a greater GH response to the GHRH+alpha-GFC than to GHRH alone. The potentiating effect of alpha-GFC on GH secretion was more pronounced in the elderly subjects. These findings confirm the observation that aged individuals respond less well to GHRH than younger subjects, and provides further evidence that increased cholinergic tone enhances GH release.
Subject(s)
Glycerylphosphorylcholine/pharmacology , Growth Hormone-Releasing Hormone/pharmacology , Growth Hormone/metabolism , Adult , Age Factors , Female , Humans , Male , Middle Aged , Parasympathetic Nervous System/drug effectsABSTRACT
Chronic treatment with LHRH analogs is known to depress testosterone (T) values to castration levels. In contrast to results from animal experiments, studies in humans indicate that a pituitary-dependent mechanism predominates in the suppression of plasma T. However, this reduction in T levels may occur when LH values are within or below the normal range. One explanation for this result has been that while absolute values of LH in serum may not change, the bioactivity of LH is reduced. The present study has been performed to determine whether this discrepancy between LH and T values is obscured by the hypersecretion of the alpha-subunit which is devoid of any biological activity but crossreacts in most RIAs with LH. Following 2 days of blood collection to establish basal serum hormone levels, six men with prostatic cancer were treated with the LHRH agonist, Buserelin (500 micrograms sc, daily injection) for 15 days. The most significant endocrine responses at the end of this treatment were as follows: 1) T levels were depressed to the castration range; 2) no change was seen in the LH values with a conventional RIA procedure which crossreacted with the alpha-subunit; 3) a significant decrease was found in the LH values evaluated with an immunoradiometric (IRMA) method, which shows no cross-reactivity with the alpha-subunit; 4) there was a significant increase in the alpha-subunit levels; and 5) serum FSH levels were significantly decreased.(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Buserelin/pharmacology , Glycoprotein Hormones, alpha Subunit/blood , Luteinizing Hormone/blood , Aged , Chromatography, Gel , Follicle Stimulating Hormone/blood , Glycoprotein Hormones, alpha Subunit/metabolism , Humans , Immunoradiometric Assay , Male , Middle Aged , Pituitary Gland/drug effects , Prostatic Neoplasms/drug therapy , Radioimmunoassay , Testis/drug effects , Testosterone/bloodABSTRACT
In order to investigate the regulatory mechanisms involved in the secretion of glycoprotein hormones, we studied the secretory patterns of LH, FSH and alpha-subunit in hypogonadal men. Three groups of patients with carcinoma of the prostate were studied both before and 15 days after orchiectomy, or the initiation of ketoconazole or LHRH analog therapy. There were significant increases (P less than 0.01) in LH and alpha-subunit levels in the patients treated with orchiectomy and ketoconazole, but FSH levels increased only in the orchiectomized patients. After LHRH analog treatment, LH levels were significantly decreased when assayed with an immunoradiometric assay method which does not cross-react with alpha-subunit. FSH values were significantly lower than pretreatment levels, while alpha-subunit levels remained significantly elevated throughout the study period. These results demonstrate that after both chemical (ketoconazole) and surgical castration, the secretion of alpha subunit follows a pattern which is tightly correlated with that of LH but not of FSH. However, after LHRH analog treatment, alpha-subunit appears to be the sole secretory product of the gonadotroph.
Subject(s)
Glycoprotein Hormones, alpha Subunit/metabolism , Orchiectomy , Aged , Animals , Glycoprotein Hormones, alpha Subunit/blood , Gonadotropin-Releasing Hormone/analogs & derivatives , Humans , Ketoconazole/pharmacology , Male , Rabbits , Radioimmunoassay , Testosterone/biosynthesis , Testosterone/bloodABSTRACT
Fourteen patients with advanced prostatic carcinoma have been considered. Some were treated with goserelin depot and some with goserelin depot plus flutamide; basal and stimulated PRL were studied in the two groups before and after two months treatment in order to verify a possible interference with prolactin secretion which seems to have a trophic and stimulating effect on neoplastic tissue growth. Basal PRL levels and levels after TRH infusion haven't shown significant variations between the two groups of patients. Even if relative to a short time, our results exclude PRL increase, which might be suspected with these drugs, and at last confirm the effectiveness of this treatment (LHRH analogs plus flutamide) in prostatic carcinoma.
Subject(s)
Adenocarcinoma/drug therapy , Anilides/therapeutic use , Buserelin/analogs & derivatives , Flutamide/therapeutic use , Prolactin/blood , Prostatic Neoplasms/drug therapy , Adenocarcinoma/blood , Aged , Aged, 80 and over , Buserelin/administration & dosage , Buserelin/therapeutic use , Delayed-Action Preparations , Drug Therapy, Combination , Goserelin , Humans , Male , Middle Aged , Prostatic Neoplasms/blood , Thyrotropin-Releasing Hormone/pharmacologySubject(s)
Surgical Procedures, Operative , Thyroglobulin/blood , Thyroid Gland/surgery , Thyroid Hormones/blood , Thyrotropin/blood , Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Thyroidectomy , Time FactorsABSTRACT
In a group of 30 obese male patients (160.2% of ideal body weight), an impaired function of the pituitary-gonadal axis has been demonstrated. Decreased testosterone and increased estradiol basal levels, increased LH and FHS responsiveness to gonadotropin-releasing hormone, and increased basal prolactin (PRL) levels are the most significant findings. The overweight factor seems to account for the documented decreased testosterone and increased estrogen levels through a modulation of peripheral steroid metabolism. These peripheral steroid patterns might affect gonadotropin and PRL secretions as well; nevertheless an interference with the metabolism of cerebral neurotransmitters, perhaps related to a nutritional component (impaired glucose tolerance), cannot be completely excluded.
Subject(s)
Obesity/physiopathology , Pituitary Gland/physiopathology , Testis/physiopathology , Adult , Chorionic Gonadotropin/blood , Estradiol/blood , Estrone/blood , Glucose Tolerance Test , Humans , Male , Prolactin/blood , Sex Hormone-Binding Globulin/analysis , Testosterone/bloodABSTRACT
Nineteen normal subjects (12 men and 7 women) were injected with 100 micrograms of ACTH 1-17. Additionally 6 male subjects were studied twice at 3-day intervals with random infusions of ACTH 1-17 and saline. A clear GH response to ACTH 1-17 infusions (GH peak higher than 5 ng/ml) was documented in 10 out of 12 males and in 6 out of 7 women. In the 6 male subjects studied twice, clear-cut GH increments were observed only after peptide administration. PRL levels decreased throughout the study period both in male and female subjects; however, when the PRL percentage decline was evaluated in the same group of subjects after saline and ACTH 1-17, the more obvious decrease of PRL levels after the peptide infusion was not statistically significant. No variation of LH, FSH and TSH levels was documented. With the exception of the specific increase of cortisol levels, no significant change in peripheral steroid pattern (Te, E2, DHEA-S) was observed. In this experiment the effect on GH secretion was quite evident in both sexes. This effect was obtained using the lowest dosage of ACTH preparation documented in the literature.