One month following carbon monoxide poisoning, a 39 year-old man developed incontinence, memory impairment, disorientation and emotional instability. He was hospitalized 7weeks later, and during hospitalization he exhibited myoclonic movements of the neck and lower limbs. He was given piracetam intravenously for 11 days. The myoclonus was significantly reduced by the third day of treatment and had disappeared by the seventh day. There was no recurrence following cessation of treatment.
Adult ; Carbon Monoxide Poisoning/complications* ; Human ; Male ; Myoclonus/drug therapy ; Myoclonus/etiology* ; Piracetam/therapeutic use* ; Pyrrolidinones/therapeutic use*

In the two decades since AZT was first approved for clinical use in 1987, 24 additional antiretroviral agents have been approved. They include 7 nucleoside analogs, a nucleotide analog and 4 non-nucleoside reverse transcriptase inhibitors, 10 protease inhibitors, 2 entry inhibitors and an integrase inhibitor. More than 20 investigational agents are currently being studied in clinical trials. Highly active antiretroviral therapy (HAART), which involves a combination of anti-HIV-1 drugs, is extremely effective in suppressing HIV-1 replication and increasing CD4+ number and results in substantial reductions in HIV-1-related morbidity and mortality. In last 20 years, much has been learned about resistance to antiretroviral drugs, drug interactions and metabolic complications of antiviral drug use. Drugs are now selected on the basis of resistance tests and on the risk of specific drug complications in individual patients. As a result, decisions about the therapy of HIV/AIDS have become personalized and are made on a patient-by-patient basis. With appropriate medical management, a person with HIV-1 now has the possibility of a nearly normal life expectancy.
Anti-HIV Agents ; adverse effects ; pharmacology ; therapeutic use ; Antiretroviral Therapy, Highly Active ; Cyclohexanes ; chemistry ; pharmacology ; therapeutic use ; Drug Resistance, Viral ; HIV Envelope Protein gp41 ; chemistry ; therapeutic use ; HIV Fusion Inhibitors ; chemistry ; pharmacology ; therapeutic use ; HIV Infections ; drug therapy ; HIV Integrase Inhibitors ; chemistry ; pharmacology ; therapeutic use ; HIV Protease Inhibitors ; chemistry ; pharmacology ; therapeutic use ; HIV Reverse Transcriptase ; chemistry ; pharmacology ; therapeutic use ; HIV-1 ; drug effects ; physiology ; Humans ; Molecular Structure ; Peptide Fragments ; chemistry ; therapeutic use ; Pyrrolidinones ; chemistry ; pharmacology ; therapeutic use ; Raltegravir Potassium ; Saquinavir ; chemistry ; pharmacology ; therapeutic use ; Triazoles ; chemistry ; pharmacology ; therapeutic use ; Virus Replication ; drug effects ; Zidovudine ; chemistry ; pharmacology ; therapeutic use

The layers of keratinocytes form an acid mantle on the surface of the skin. Herein, we investigated the effects of acidic pH on the membrane current and [Ca2+](c) of human primary keratinocytes from foreskins and human keratinocyte cell line (HaCaT). Acidic extracellular pH (pHe< or =5.5) activated outwardly rectifying Cl- current (I(Cl,pH)) with slow kinetics of voltage-dependent activation. I(Cl,pH) was potently inhibited by an anion channel blocker 4,4`-diisothiocyanostilbene-2,2`-disulphonic acid (DIDS, 73.5% inhibition at 1micrometer). I(Cl,pH) became more sensitive to pHe by raising temperature from 24degrees C to 37degrees C. HaCaT cells also expressed Ca2+ -activated Cl- current (I(Cl,Ca)), and the amplitude of I(Cl,Ca) was increased by relatively weak acidic pHe (7.0 and 6.8). Interestingly, the acidic pHe (5.0) also induced a sharp increase in the intracellular [Ca2+] (delta[Ca2+](acid)) of HaCaT cells. The delta[Ca2+](acid) was independent of extracellular Ca2+, and was abolished by the pretreatment with PLC inhibitor, U73122. In primary human keratinocytes, 5 out of 28 tested cells showed delta[Ca2+](acid). In summary, we found I(Cl,pH) and delta[Ca2+](acid) in human keratinocytes, and these ionic signals might have implication in pathophysiological responses and differentiation of epidermal keratinocytes.
Cell Line ; Estrenes ; Foreskin ; Humans ; Hydrogen-Ion Concentration ; Keratinocytes ; Kinetics ; Membranes ; Pyrrolidinones ; Skin

A novel cornea tissue scaffold material was prepared with N-vinly pyrrolidome (NVP) and a biodegradable crosslinking agent by radical polymerization, using azoisobutyronitrile (AIBN) as initiator. Water absorption test and contact angle measure were conducted, and the degradation process of material was investigated. The biocompatibility evaluation was carried out by implantation of material in the rabbits, and by cell culture. The water absorption was over 104%, the contact angle was lower than 41degrees, and the degradation speed in vitro kept steady. The results of implantation in the rabbits showed that the material was almost degraded 3 months later and lots of collagen and cornea stroma cells appeared in it,but there was no inflammation around it. The result of epithelial cells culture showed that the cells conglutinated on the material, but no remarkable cytotoxicity was noted.
Animals ; Biocompatible Materials ; chemistry ; Cornea ; cytology ; Epithelium, Corneal ; cytology ; Materials Testing ; Nitriles ; chemistry ; Prostheses and Implants ; Pyrrolidinones ; chemistry ; Rabbits ; Tissue Engineering

OBJECTIVETo study the chemical constituents in roots of Saussurea lappa.

METHODIsolation and purification were carried out by silica gel, Sephadex LH-20 and RP-18 column chromatography. The chemical structures of constituents were elucidated on the basis of spectral data.

RESULTEleven compounds were isolated and identified as: 5,7-dihydroxy-2-methylchromone (1), p-hydroxybenzaldehyde (2), 3,5-dimethoxy-4-hydroxy-benzaldehyde (3), 3,5-dimethoxy-4-hydroxy-acetophenone (4), ethyl 2-pyrrolidinone-5(s)-carboxylate (5), 5-hydroxymethyl-furaldehyde (6), palmitic acid (7), succinic acid (8), glucose (9), daucosterol (10), beta-sitosterol (11).

CONCLUSIONCompounds 1, 2, 4, 5, 7, 9 were isolated from the genus Saussurea for the first time.

Benzaldehydes ; chemistry ; isolation & purification ; Palmitic Acid ; chemistry ; isolation & purification ; Plant Roots ; chemistry ; Pyrrolidinones ; chemistry ; isolation & purification ; Saussurea ; chemistry ; Sitosterols ; chemistry ; isolation & purification

OBJECTIVETo observe the clinical efficacy of modified Huanglian Wendan Decoction (HWD) in treating senile mild cognitive impairment (MCI) of turbid-phlegm blocking orifice syndrome.

METHODSWith a block randomized, double-blinded and controlled design adopted, the 64 patients of MCI selected from December 2007 to February 2009 were randomly and equally assigned to two groups. The treatment group was treated with HWD in dose of 200 mL, twice a day; the control group was given Aniracetam 0.2 g (for patients over 70-years-old, 0.1 g) three times a day. And the illusive medicine in dosage-form of capsule/decoction simulated to that used in the opposite group was applied. The medication and observation lasted for three months. Chinese medicine syndrome, cognition capacity (by MMSE), laboratory indexes [acetylcholine (Ach), superoxide dismutase (SOD), malondialdehyde (MDA)] and safety related indexes in patients were observed.

RESULTSAfter treatment, MMSE score increased in both groups, but the increment in the treatment group was significantly higher than that in the control group (P<0.01); Chinese medicine syndrome estimated by scoring showed that after treatment, all scores of syndromes, excepting the expectoration, were improved in the treatment group with the post-treatment scores significantly lower than those in the control group respectively (P<0.05 or P<0.01); while in the control group, lowering of scores only showed in some symptoms such as poor memory, heavy head or dizziness, and heavy sensation in limbs and body. Serum levels of Ach and SOD decreased and MDA increased in both groups after treatment, but the change of Ach was more significant in the treatment group (P<0.01). No obvious adverse reactions were found during the treatment.

CONCLUSIONFor treatment of MCI, HWD shows effects in improving patients' symptoms, cognition capacity and elevating serum Ach content better than that of Aniracetam; and with effects for raising SOD activity and reducing MDA level similar to those of Aniracetam.

Aged ; Aged, 80 and over ; Cognitive Dysfunction ; diagnosis ; drug therapy ; Double-Blind Method ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Pyrrolidinones ; therapeutic use

The calcium-activated K+ (BKCa) channel is one of the potassium-selective ion channels that are present in the nervous and vascular systems. Ca2+ is the main regulator of BKCa channel activation. The BKCa channel contains two high affinity Ca2+ binding sites, namely, regulators of K+ conductance, RCK1 and the Ca2+ bowl. Lysophosphatidic acid (LPA, 1-radyl-2-hydroxy-sn-glycero-3-phosphate) is one of the neurolipids. LPA affects diverse cellular functions on many cell types through G protein-coupled LPA receptor subtypes. The activation of LPA receptors induces transient elevation of intracellular Ca2+ levels through diverse G proteins such as Galphaq/11, Galphai, Galpha12/13, and Galphas and the related signal transduction pathway. In the present study, we examined LPA effects on BKCa channel activity expressed in Xenopus oocytes, which are known to endogenously express the LPA receptor. Treatment with LPA induced a large outward current in a reversible and concentration-dependent manner. However, repeated treatment with LPA induced a rapid desensitization, and the LPA receptor antagonist Ki16425 blocked LPA action. LPA-mediated BKCa channel activation was also attenuated by the PLC inhibitor U-73122, IP3 inhibitor 2-APB, Ca2+ chelator BAPTA, or PKC inhibitor calphostin. In addition, mutations in RCK1 and RCK2 also attenuated LPA-mediated BKCa channel activation. The present study indicates that LPA-mediated activation of the BKCa channel is achieved through the PLC, IP3, Ca2+, and PKC pathway and that LPA-mediated activation of the BKCa channel could be one of the biological effects of LPA in the nervous and vascular systems.
Binding Sites ; Egtazic Acid ; Estrenes ; GTP-Binding Proteins ; Ion Channels ; Isoxazoles ; Lysophospholipids ; Naphthalenes ; Oocytes ; Potassium ; Potassium Channels ; Propionates ; Pyrrolidinones ; Receptors, Lysophosphatidic Acid ; Signal Transduction ; Xenopus

AIMTo prepare dilitazem hydrochloride delayed-onset, sustained release tablet, which can not only provide the delay in release start, but also the constant release rate after a lag time. To analyze release mechanism and investigate the effect of outershell compositions on release behavior.

METHODSThe delayed-onset, sustained release tablets were prepared by dry-compression coated technology. The release profiles of uncoated cores and presscoated tablets were compared. Two parameters, time-lag (Tlag) and release rate (k), were used to evaluate the influence of factors, such as the amount of hydroxypropylmethylcellulose (HPMC) and poly-vinyl-pyrrolidinone (PVP) K30, the viscosity of ethylcellulose (EC) and HPMC, and the compression load on diltazam hydrochloride (DIL) release. Higuchi equation and Peppa's equation were used to analyze release mechanism.

RESULTSWith the increase of HPMC amount or HPMC viscosity, Tlag was prolonged and k was decreased; With the increase of PVP K30 amount, Tlag was shortened and k was increased; EC viscosity and compression load above certain degree showed no effect on DIL release.

CONCLUSIONThe drug release from delayed-release tablet is controlled by erosion mechanism, Tlag is determined by the erosion rate of outer-shell.

Cellulose ; chemistry ; Delayed-Action Preparations ; Diltiazem ; administration & dosage ; Lactose ; analogs & derivatives ; chemistry ; Methylcellulose ; analogs & derivatives ; chemistry ; Oxazines ; Polyvinyls ; chemistry ; Pyrrolidinones ; chemistry ; Tablets ; administration & dosage ; chemistry ; Technology, Pharmaceutical ; Viscosity

OBJECTIVETo investigate the effects of fluorochloridone (FLC) exposure on the testes of adult Sprague-Dawley (SD) rats.

METHODSForty male SD rats were randomly divided into four groups. These groups, each of 10 male rats, were separately given FLC by gavage at a dose of 0 (control), 30, 150, or 750 mg/kg once daily for 28 d. The oxidative stress biomarkers in the testes were measured by spectrophotometry. The pathological changes in testicular tissues were evaluated under the light and electric microscopes. The cauda epididymal sperm count was determined. The testicular toxicity of FLC was assessed accordingly.

RESULTSCompared with the control group, the 750 mg/kg FLC group had significantly lower testicular weight and organ coefficient, epididymal weight, and cauda epididymal sperm count (P < 0.05 or P < 0.01), the 150 and 750 mg/kg FLC groups had significantly increased malonaldehyde content (P < 0.05 or P < 0.01), each exposed group had a significantly reduced glutathione (GSH) level (P < 0.05 or P < 0.01), the 750 mg/kg FLC group had significantly reduced activities of superoxide dismutase (SOD), catalase (CAT), GSH peroxidase, GSH S-transferase (GSH-ST), and GSH reductase (GSH-GR) (P < 0.05 or P < 0.01), the 150 mg/kg FLC group showed significant decreases in the activities of all antioxidant enzymes except GSH-GR (P < 0.05 or P < 0.01), and the 30 mg/kg FLC group showed significant decreases in the activities of SOD and CAT (P < 0.05 or P < 0.01). Furthermore, seminiferous epithelial degeneration, Sertoli cell vacuolization, spermatogenic cell loss, and nuclear damage were observed under the light and electronic microscopes in the 150 and 750 mg/kg FLC groups.

CONCLUSIONFLC could damage the testes of adult rats by inducting oxidative stress. This research provided clues and directions for further exploration of the mechanism of FLC testicular toxicity.

Animals ; Male ; Oxidative Stress ; drug effects ; Pyrrolidinones ; toxicity ; Rats ; Rats, Sprague-Dawley ; Sperm Motility ; drug effects ; Testis ; drug effects ; metabolism ; pathology

OBJECTIVETo explore the role of phospholipase C-gamma1 (PLC-gamma1) signaling pathway in H(2)O(2)-induced apoptosis of PC12 cells.

METHODSPC12 cells were exposed to 50 micromol/L H(2)O(2) after pretreatment with 10 micromol/L U73122, a specific PLC-gamma1 inhibitor. Hoechst/PI double staining was performed to observe the morphological changes of the cells under light microscope. MTT assay was used to evaluate the cell viability, and the percentage of apoptotic cells was analyzed by flow cytometry. DNA fragmentation assay was carried out to characterize the cell apoptosis.

RESULTSAfter inhibition of the PLC-gamma1 signaling pathway with 10 micromol/L U73122, PC12 cells showed obvious apoptotic morphology, the viable cells decreased significantly, and the percentage of apoptotic cells rose to 35.7%. PC12 cells treated with U73122 presented with a distinct DNA ladder on electrophoresis resulting from DNA cleavage in the apoptotic cells.

CONCLUSIONPLC-gamma1 signaling pathway plays an important protective role in H(2)O(2)-induced PC12 cell apoptosis.

Animals ; Apoptosis ; drug effects ; Estrenes ; pharmacology ; Hydrogen Peroxide ; pharmacology ; PC12 Cells ; Phospholipase C gamma ; antagonists & inhibitors ; metabolism ; Pyrrolidinones ; pharmacology ; Rats ; Signal Transduction