Subacute Combined Degeneration of the Spinal Cord Induced by Nitrous Oxide Abuse: A Rare Patient Presentation to a Spine Surgery Clinic: Illustrative Case.

Subacute combined degeneration (SCD) of the spinal cord is a disease involving the lateral and posterior columns of the spinal cord that can manifest in patients with vitamin B12 deficiency. Nitrous oxide (N2O)-induced SCD of the spinal cord is a result of N2O interfering with the metabolism of vitamin B12 and results in nervous system demyelination. This is an infrequent complication of N2O anesthesia; however, cases are rising with recreational N2O use. This case report describes a patient with SCD of the spinal cord induced by recreational N2O abuse. The patient presented to a spine surgery clinic with a 3-week history of progressive global weakness and paresthesias. After a detailed history and physical examination, the diagnosis was made and supported by various tests and imaging findings. Despite marked neurologic deficits, the patient's symptoms improved markedly with therapy and vitamin B12 supplementation. Spine surgery clinicians may be confronted with these cases and should be aware of this atypical presentation of SCD. As in our case, patients may present with neurologic deficits of unclear etiology. Neurologic dysfunction may be irreversible; therefore, accurate diagnosis, medical treatment, and complete neurologic evaluation are of the utmost importance to prevent additional progression.

Methanolic fruit extract of Myrica nagi protects the hypothalamus and attenuates inflammation associated with gold thioglucose- and high-fat diet-induced obesity via various adipokines.

BACKGROUND: Myrica nagi is popular in unani and ayurveda. Chemical constituents like myricetin isolated from its fruit has been shown to exert beneficial effects against cardiovascular disease, cancer, inflammatory conditions, and metabolic disorders. OBJECTIVES: This study aimed to elucidate the anti-obesity effect of the methanolic extract of M. nagi (MEMN) using in vivo animal models of obesity induced by gold thioglucose or a high-fat diet. MATERIALS AND METHODS: The obese mice were treated or untreated with MEMN for 8 weeks. Thereafter, feed intake, Lee index, and body mass index (BMI); biochemical parameters such as lipid profile, liver enzymes and specific biomarkers of obesity, including insulin, leptin, adiponectin, free fatty acids (FFA), monocyte chemoattractant protein (MCP)-1, and resistin, were recorded. The weight and histopathology of organs and fat tissue were examined to validate the effectiveness of the extract. RESULTS: MEMN administration at various doses significantly reduced the induced weight gain, feed intake, BMI, and Lee index. Adipose tissue decreased as the MEMN dose increased. MEMN attenuated liver enzyme activity, decreased lipid, leptin, MCP-1, resistin, and FFA levels, and increased adiponectin levels. It also increased protection of liver cells and decreased accumulation of mesenteric fat. CONCLUSIONS: MEMN supplementation decreased weight and improved obesity serum/plasma lipid biomarker, insulin, leptin, adiponectin, MCP-1, and resistin levels. The weight-reducing activity of MEMN may be mediated by decreased gastrointestinal fat absorption and modulation of inflammation associated signaling pathways, leading to reduced adipose inflammation associated with energy expenditure.

How do pharmacists in English general practices identify their impact? An exploratory qualitative study of measurement problems.

BACKGROUND: In England, there is an ongoing national pilot to expand pharmacists' presence in general practice. Evaluation of the pilot includes numerical and survey-based Key Performance Indicators (KPIs) and requires pharmacists to electronically record their activities, possibly by using activity codes. At the time of the study (2016), no national evaluation of pharmacists' impact in this environment had been formally announced. The aim of this qualitative study was to identify problems that English pharmacists face when measuring and recording their impact in general practice. METHODS: All pharmacists, general practitioners (GPs) and practice managers working across two West London pilot sites were invited, via e-mail, to participate in a focus group study. Appropriately trained facilitators conducted two audio-recorded, semi-structured focus groups, each lasting approximately 1 h, to explore experiences and perceptions associated with the KPIs. Audio-recordings were transcribed verbatim and the data analysed thematically. RESULTS: In total, 13 pharmacists, one GP and one practice manager took part in the study. Four major themes were discerned: inappropriateness of the numerical national KPIs ("whether or not we actually have positive impact on KPIs is beyond our control"); depth and breadth of pharmacists' activity ("we see a huge plethora of different patients and go through this holistic approach - everything is looked at"); awareness of practice-based pharmacists' roles ("I think the really important [thing] is that everyone knows what pharmacists in general practice are doing"); and central evaluation versus local initiatives ("the KPIs will be measured by National Health Service England regardless of what we think" versus "what I think is more pertinent, are there some local things we're going to measure?"). CONCLUSIONS: Measures that will effectively capture pharmacists' impact in general practice should be developed, along with a set of codes reflecting the whole spectrum of pharmacists' activities. Our study also points out the significance of a transparent, robust national evaluation, including exploring the needs/expectations of practice staff and patients regarding pharmacists' presence in general practice.

Khat (Catha edulis Forsk) - And now there are three.

For centuries, a large number of people living in the southwestern part of the Arabian Peninsula and eastern Africa have chewed the fresh leaves and twigs of the plant Catha edulis Forsk, more commonly known as khat, for its psychostimulatory effect. The main active compound in khat is cathinone, whose synthetic derivatives form a part of the new psychoactive substances list. This review summaries the prevalence of khat use, its harvesting and consumption, the biosynthetic pathway in khat, the mechanism of action, the results from animal and human studies, and its dependence potential. It is unlikely that khat use will be prohibited in countries where it is traditionally consumed and socially acceptable unlike in other countries of the world where both the importation and the consumption of khat and cathinone is banned. Khat users being mainly Muslims prohibited from using alcohol or other drugs probably represent the largest global number of mono-drug users of an amphetamine-like stimulant. Thus, khat use represents a unique situation and a neglected area of research in Africa.

Antinocieptive and anti-inflammatory effects of Toddalia asiatica (L) Lam. (Rutaceae) root extract in Swiss albino mice.

INTRODUCTION: Toddalia asiatica is a commonly used medicinal plant in East Africa for the management of pain and inflammatory conditions. The present study investigated the antinociceptive and the anti-inflammatory effects of T. asiatica in Swiss albino mice. METHODS: The antinociceptive and the anti-inflammatory effects of T. asiatica were investigated using formalin-induced pain test and the carrageenin-induced oedema paw. The extract solvent (vehicle), aspirin and indomethacin were employed as negative and positive controls respectively. Eight mice were used in each experiment. RESULTS: In the early phase of the formalin test, the 100mg/kg dose showed no significant antinociceptive activity while the 200mg/kg showed significant (p < 0.01) antinociceptive activity. The 100 mg/kg dose showed highly significant antinociceptive activity (p < 0.001) in the late phase of the formalin test while the 200mg/kg dose showed no significant antinociceptive activity. A reduction in carragenin induced acute inflammation paw oedema was significant (p < 0.01) following administration of 100mg/kg dose but not with the 200mg/kg dose. CONCLUSION: The present study therefore lends support to the anecdotal evidence for use of T. asiatica in the management of painful and inflammatory conditions.

Study on the mechanism of the bronchodilatory effects of Cynodon dactylon (Linn.) and identification of the active ingredient.

ETHNOPHARMACOLOGICAL RELEVANCE: In the traditional medicine, Cynodon dactylon (Linn.) is used in asthma, but scientific studies to provide evidence for medicinal uses are sparse. Thus this study was undertaken to provide evidence for medicinal use in asthma as a bronchodilator, and to identify active ingredient(s). MATERIALS AND METHODS: In vivo, acetylcholine (Ach)-induced bronchospasm was conducted in guinea pig while isolated rat tracheal strip was suspended in organ bath to measure the concentration response curve using multichannel data acquisition system. RESULTS: The chloroform extract of Cynodon dactylon (CECD) protected against Ach-induced bronchospasm in guinea pigs, similar to atropine. In the in vitro studies, CECD relaxed carbachol (CCh) and high K+-induced contraction of rat tracheal strip, similar to atropine and verapamil respectively, suggesting antimuscarinic and calcium channel blocking (CCB) activities, which were confirmed by right ward shifting of CCh and Ca(+2) concentration response curve (CRC). The phosphodiestrase (PDE) inhibitory activity was confirmed by potentiation of isoprenaline-induced inhibitory response, similar to papaverine. Densitometry analyses led to the identification of scopoletin as an active ingredient. Effectively, it significantly inhibited high K+, and Ca(+2) induced contractile response, similar to verapamil. The phosphodiestrase (PDE) inhibitory activity was confirmed by direct evidence of potentiation of isoprenaline-induced inhibitory response, similar to papaverine. CONCLUSIONS: These results suggest that the bronchodilator activity of CECD is partly due to presence of scopoletin, and mediated possibly through CCB and PDE inhibition.

A dynamic metabolic flux balance based model of fed-batch fermentation of Bordetella pertussis.

A mathematical model based on a dynamic metabolic flux balance (DMFB) is developed for a process of fed-batch fermentation of Bordetella pertussis. The model is based on the maximization of growth rate at each time interval subject to stoichiometric constraints. The model is calibrated and verified with experimental data obtained in two different bioreactor experimental systems. It was found that the model calibration was mostly sensitive to the consumption or production rates of tyrosine and, for high supplementation rates, to the consumption rate of glutamate. Following this calibration the model correctly predicts biomass and by-products concentrations for different supplementation rates. Comparisons of model predictions to oxygen uptake and carbon emission rates measurements indicate that the TCA cycle is fully functional.

Synthesis and evaluation of anti-inflammatory, analgesic, ulcerogenic and lipid peroxidation properties of new 2-(4-isobutylphenyl)propanoic acid derivatives.

Synthesis and pharmacological evaluation of various 2-(4-isobutylphenyl)propanoic acid derivatives containing 1,3,4-thiadiazole and thiadiazolo[3,2-a][1,3,5]triazine-5-thione nucleus is reported here. The structures of new compounds are supported by IR, (1)H & (13)C NMR data. These compounds were tested in vivo for their anti-inflammatory activity. The compounds which showed activity comparable to the standard drug ibuprofen were screened for their analgesic, ulcerogenic and lipid peroxidation activities. The compounds, which showed less ulcerogenic action, also showed reduced malondialdehyde production (MDA). Compound 4i and 5f showed 89.50 and 88.88% of inhibition in paw edema, 69.80 and 66.25% protection against acetic acid-induced writhings and 0.7 and 0.65 of severity index, respectively, compared to 90.12, 72.50 and 1.95 values of ibuprofen.

Bile salt composition is secondary to bile salt concentration in determining hydrocortisone and progesterone solubility in intestinal mimetic fluids.

Simulated intestinal fluids (SIFs) used to assay the solubility of orally administered drugs are typically based on a single bile salt; sodium taurocholate (STC). The aim of this study was to develop mimetic intestinal fluids with a closer similarity to physiological fluids than those reported to date by developing a mixed bile salt (MBS) system (STC, sodium glycodeoxycholate, sodium deoxycholate; 60:39:1) with different concentrations of lecithin, the preponderant intestinal phospholipid. Hydrocortisone and progesterone were used as model drugs to evaluate systematically the influence of SIF composition on solubility. Increasing total bile salt concentration from 0 to 30 mM increased hydrocortisone and progesterone solubility by 2- and ∼25-fold, respectively. Accordingly, higher solubilities were measured in the fed-state compared to the fasted-state SIFs. Progesterone showed the greatest increases in solubility in STC and MBS systems (2-7-fold) compared to hydrocortisone (no significant change; P>0.05) as lecithin concentration was increased. Overall, MBS systems gave similar solubility profiles to STC. In conclusion, the addenda of MBS and lecithin were found to be secondary to the influence of BS concentration. These data provide a foundation for the design of more bio-similar media for pivotal decision-guiding assays in drug development and quality control settings.

Proconvulsant effect of khat (Catha edulis) in Sprague dawley rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Catha edulis (khat) is a plant whose fresh young leaves are used by an estimated five million people in eastern Africa and the Arabian Peninsula as a drug of recreation. The fresh leaves and shoots are rich in cathinone, a psychostimulant with effects similar to those of amphetamines. Psychostimulants produce a dose-related excitation of the central nervous system which can lead to seizures and convulsions. However there are no reports on studies of the effect of this herb on brain excitability and seizures. This knowledge is useful for doctors who may prescribe drugs whose side effects include lowering seizure threshold because there could be additive proconvulsant effect among khat users. AIM OF THE STUDY: to determined whether khat lowers pentylenetetrazole (PTZ) seizure threshold. METHODOLOGY: Male Sprague dawley rats were given fresh aqueous khat extract, old aqueous khat extract (3 g/kg bw), methylphenidate or saline and the timed intravenous (PTZ) seizure threshold test was used to study its effect on seizure threshold. RESULTS: Fresh khat (3 g/kg) and methylphenidate (4 mg/kg) lowered PTZ seizure threshold. CONCLUSION: Khat lowers seizure threshold.

Cytomorphologic features of primary peritoneal mesothelioma in effusion, washing, and fine-needle aspiration biopsy specimens: examination of 49 cases at one institution, including post-intraperitoneal hyperthermic chemotherapy findings.

Primary peritoneal mesotheliomas (PPMs) are rare tumors of adults. At our institution, PPMs are treated with a combination of cytoreductive surgery and intraperitoneal hyperthermic chemotherapy (IPHC) in appropriate patients. We present a summary of cytologic features of PPM in 49 positive (malignant) specimens during a 15-year period at 1 institution. Of the corresponding 49 PPM histologic specimens, 46 were epithelial, 2 sarcomatoid, and 1 multicystic mesothelioma. This includes our experience with washing specimens obtained from patients with PPM following treatment with cytoreductive surgery combined with IPHC. The rarity of PPM makes this neoplasm unfamiliar to most pathologists. However, cytologic features can be diagnostic in a majority of cases. We present a summary of cytologic features that, in our experience, we find to be most useful in making or excluding a diagnosis of PPM. To our knowledge, this is the first large series reporting the cytomorphologic features of PPM in peritoneal effusions, pelvic washing specimens, and infradiaphragmatic fine-needle aspiration biopsy specimens.

In vitro study of the effects of khat (Catha edulis Forsk) extract on isolated mouse interstitial cells.

Isolated mouse interstitial cells were incubated with different concentrations of khat (Catha edulis) extract (0.06 mg/ml, 0.6 mg/ml, 6 mg/ml, 30 mg/ml and 60 mg/ml) and cell viability as well as testosterone concentration measured at 30 min intervals over a 3h incubation period. High concentrations of khat extract (30 mg/ml and 60 mg/ml) significantly inhibited testosterone production while low concentrations (0.06 mg/ml, 0.6 mg/ml and 6 mg/ml) significantly stimulated (P<0.05) testosterone production by mouse interstitial cells. Similarly, at concentrations of 30 mg/ml and 60 mg/ml, there was a significant decrease in interstitial cell viability, whereas at 0.06 mg/ml, 0.6 mg/ml and 6 mg/ml there was no significant decrease. There was only a weak correlation (r=0.39) between testosterone production and viable interstitial cells. We postulate that khat extract at high concentrations may cause reproductive function impairment in the user but at low concentrations, may enhance testosterone production with accompanying effects on reproductive functions in male mice.