Love potions and the ointment of witches: historical aspects of the nightshade alkaloids

BACKGROUND: Nightshade plants (Solanaceae) have been utilized as hallucinogenic drugs since antiquity in nearly every culture. The Solanaceae alkaloids, atropine and scopolamine, were the active substances in ointment of witches and medieval anesthetics, and in modern poisons. They are still currently used as hallucinogenic drugs. In poisonings, a dosage- and substance-dependent clinical picture occurs, with central and peripheral symptoms. Hallucinations are predominant in the middle dose range, which explains the drugs' earlier utilization for religious and prophetic purposes. Respiratory depression and arrest at high doses confirm the use of scopolamine as a lethal poison. Despite this, the nightshade alkaloids were utilized in clinical medicine in the 19th century. This is an overview of the cultural history of the nightshade alkaloids.     

Clear lens extraction and implantation of negative-power posterior chamber intraocular lenses to correct extreme myopia

PURPOSE: To evaluate the effectiveness, predictability, and safety of clear lens extraction to correct extreme myopia. SETTING: Clinica de Nuestra Se?ora de la Concepción, Fundación Jiménez Díaz, Madrid, Spain. METHODS: This retrospective study comprised 26 eyes of 17 highly myopic patients who had clear lens extraction and implantation of a negative-power posterior chamber intraocular lens (IOL). The IOL power was calculated using the SRK/T formula. Analyzed were visual and refractive results and intraoperative and postoperative complications. Follow-up was at least 12 months in all cases. RESULTS: Uncorrected visual acuity improved in all cases, with 80.77% of eyes achieving 20/100 or better and 42.30%, 20/40 or better. Best spectacle-corrected visual acuity (BSCVA) improved in 23 eyes (88.46%). The percentage of eyes achieving a BSCVA of 20/100 or better increased from 73.07% preoperatively to 92.30% postoperatively and the percentage achieving 20/40 or better, from 23.07 to 73.07%. Of the 26 eyes, 76.91% were within 1.00 diopter (D) of refractive error and 96.16% were within 2.00 D. No intraoperative complications occurred. Although postoperatively 3 eyes (11.53%) developed choroidal detachment and 5 (19.23%) had an intraocular pressure greater than 25 mm Hg, all had a favorable outcome. Four eyes (15.38%) developed posterior capsule opacification and had a neodymium:YAG laser posterior capsulotomy 6 months postoperatively. No retinal detachments were observed. CONCLUSION: Clear lens extraction with negative-power IOL implantation using the SRK/T formula had good effectiveness, acceptable predictability, and a low morbidity in eyes with extreme myopia over a short follow-up. A longer follow-up with more cases is needed to assess the safety of the procedure.     

Enantioselective synthesis and pharmacology of 11-hydroxy-(1'S,2'R)-dimethylheptyl-delta 8-THC

An enantioselective synthesis of the (1'S,2'R)-dimethylheptyl cannabinoid side chain has been developed and employed in the synthesis of 11-hydroxy-(1'S,2'R)-dimethylheptyl-delta 8-THC (3). Pharmacology, in vivo and in vitro, indicate (3) to be one of the most potent traditional cannabinoids known.     

Delta opioid peptide [D-Ala2,D-leu5]enkephalin blocks the long-term loss of dopamine transporters induced by multiple administrations of methamphetamine: involvement of opioid receptors and reactive oxygen species

Delta opioid peptide [D-Ala2,D-leu5]enkephalin (DADLE) can prolong organ preservation and increases myocardial tolerance to ischemia. Our study examined the protective property of DADLE against methamphetamine- (METH) induced dopaminergic terminal damage in the central nervous system. Because the neurotoxicity of METH involves reactive oxygen species, we also examined if DADLE might be an antioxidative agent in vitro. DADLE at 2 and 4 mg/kg (i.p.), given 30 min before each METH administration (5 or 10 mg/kg, i.p., four injections in a day at 2-hr intervals), dose-dependently blocked the METH-induced long-term dopamine transporter loss. The opioid antagonist naltrexone blocked this action of DADLE in both aspects of striata but tends not to affect the effects of DADLE in the nucleus accumbens. DADLE did not alter changes in body temperature induced by METH. The reduction of striatal dopaminergic content and tyrosine hydroxylase activity caused by METH, however, were not blocked by DADLE. In vitro, DADLE was approximately equipotent to glutathione in inhibiting both superoxide anion formation induced by xanthine oxidase and hydroxyl radical formation evoked by ferrous/citrate complex. DADLE was only slightly less potent than glutathione in inhibiting the iron/ascorbate-induced brain lipid peroxidation. These results suggest that DADLE can protect the terminal membranes of dopaminergic neurons against METH-induced insult but not the loss of dopaminergic content and tyrosine hydroxylase activity and that this action of DADLE might involve opioid receptors as well as the sequestration of free radical.     

Conceptus, progesterone, and breed effects on uterine protein secretion in swine

This experiment consisted of the following treatment-breed groups: 1) White crossbred gilts, 2) White crossbred gilts treated with progesterone (200 mg/d in corn oil given on d 2 and 3 after estrus), and 3) Chinese Meishan gilts. Pregnant and nonpregnant gilts (n=3 to 6) from each treatment-breed combination were assigned to be slaughtered on d 10, 11, 12, 13, and 15. At slaughter each uterine horn was flushed with 20 mL of minimal essential medium. Uterine flushings were assayed for total protein, acid phosphatase, uteroferrin, retinol-binding protein, and oxytocin. Uterine flush total protein was increased by progesterone treatment, was unaffected by pregnancy status, and was less in Meishans. Similar patterns were found for retinol binding protein and uteroferrin, except that uteroferrin was greater in pregnant than in nonpregnant gilts. Oxytocin was greater in pregnant than in nonpregnant gilts, was not influenced by progesterone treatment, and was similar in Meishan and in White crossbred gilts. These results indicate that the conceptus does not influence secretion of either total protein or retinol binding protein during pregnancy and that the onset of secretion of these uterine proteins may be controlled by progesterone. The presence of the conceptus is associated with increased uteroferrin and oxytocin production. The decreased secretion of uterine proteins in Meishan gilts may partially explain the slower embryonic development that has been reported for this breed.     

Diagnostic focus on the child with myoclonic seizures in isolation or associated with other types of seizures

Myoclonus may be observed in children with mild or severe epileptic syndromes. Both types are seen at characteristic ages, together with other factors: aetiology, family history, hereditary pattern, effect on psychomotor development and EEG-EMG findings. In children with progressive or degenerative encephalopathies and myoclonus, better known as progressive myoclonic epilepsy, there are also specific clinical data, together with biological and genetic markers which permit identification. The most specific clinical characteristics of each of these clinical pictures are described, as are the complementary tests which permit confirmation of these diagnoses.     

La?nnec, re-inventor of the stethoscope?

According to our common medical culture, some facts are simply unquestionable, for instance La?nnec invented the stethoscope. But was he the first one? On a recent trip to Egypt we visited the temple of Kom Ombo, built prior to the roman period and renowned as a medical care center. Today, the tourist is fascinated by the magnificent hieroglyphics on the well-preserved walls testifying to significant advances in various fields of medicine including ophthalmology and gynecology. We were particularly interested by the basreliefs presenting vivid drawings of some of the first medical instruments. We easily identified curettes, scissors, a balance, forceps for dental extraction, and a surgical saw, but were captivated by two other instruments. The first one looked a lot like what La?nnec invented around 1820. The second one was amazingly similar to the instrument we use everyday, with a distal opening and flexible tubes (woven papyrus?) leading to proximal ear pieces. Our Egyptian guide was formal: the stethoscope was invented in Egypt. The scientific impact of our observations leaves something to be desired, but did make us think about the huge gap between the advancement of medical knowledge in ancient Egypt and La?nnec's (re)-invention. Exposed to a similar gap in history, what would our documents stored on CD and video tapes have to say to future touring doctors?     

The STOP-NIDDM Trial: an international study on the efficacy of an alpha-glucosidase inhibitor to prevent type 2 diabetes in a population with impaired glucose tolerance: rationale, design, and preliminary screening data. Study to Prevent Non-Insulin-Dependent Diabetes Mellitus

OBJECTIVE: To describe the rationale and design, and to discuss the preliminary screening data, of the Study to Prevent NIDDM (STOP-NIDDM Trial), an international study on the efficacy of the alpha-glucosidase inhibitor acarbose in preventing or delaying the development of type 2 diabetes in a population with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: A total of 1,418 subjects diagnosed with IGT according to the World Health Organization's criteria and having a fasting plasma glucose concentration > or =5.6 mmol/L were randomized in a double-blind fashion to receive either acarbose (100 mg t.i.d.) or placebo for a predictive median follow-up period of 3.9 years. The primary outcome is the development of type 2 diabetes diagnosed using a 75-g oral glucose tolerance test according to the new criteria. The secondary outcomes are changes in blood pressure, lipid profile, insulin sensitivity, cardiovascular events, and morphometric profile. RESULTS: Screening was performed in a high-risk population. As of 1 March 1997, 4,424 subjects had been screened, and data were available for 3,919 (88.5%) subjects. Of these subjects, 1,200 (30.6%) had glucose intolerance. Of the subjects with glucose intolerance, 521 (13.3%) had previously undetected type 2 diabetes, and 679 (17.3%) had IGT. Of the IGT population, 412 (60.7%) subjects were eligible for the study This population had the following characteristics: the mean age was 54.8 years, 52% of the subjects were female, 53% had more than one risk factor for type 2 diabetes, >90% had a family history of diabetes, 78.2% had a BMI > or =27 kg/m2, 47.5% had high blood pressure, 51.2% had dyslipidemia, and 22.8% of the women had a history of gestational diabetes. CONCLUSIONS: Screening of a high-risk population yields one eligible subject per every 10 volunteers screened. This study should definitely answer the question of whether acarbose can prevent or delay the progression of IGT to type 2 diabetes mellitus.     

Improved left ventricular endocardial border delineation and opacification with OPTISON (FS069), a new echocardiographic contrast agent. Results of a phase III Multicenter Trial

We investigated whether changes in iron metabolism and the transferrin receptor (TRF-R) expression were involved in the antileukaemic effects of arabinoside cytosine (ara-C). Treatment with 100 nM ara-C for 48h reduced thymidine uptake and increased the surface expression of the TRF-R on leukaemic blasts derived from 13/16 (81%) patients and on the HL-60 and U-937 cell lines. Whereas intracellular non-haem iron was strongly depleted 24 h after ara-C addition, TRF-R up-regulation and recovery of intracellular non-haem iron concentration occurred together after a longer exposure of the cultured cells to the drug. Since iron is an essential regulator of cell proliferation we have evaluated the effects of the combination between ara-C and the iron chelator desferioxamine (DSF) on the growth of HL-60 and U-937 cells. We found that desferioxamine strongly potentiated the effects of ara-C on leukaemic cell growth inhibition and apoptosis. This is the first report of a positive interaction between ara-C and an iron chelator in terms of antileukaemic effects.