Gabapentinoids comprise the medications gabapentin and pregabalin. These were designed to not onl... more Gabapentinoids comprise the medications gabapentin and pregabalin. These were designed to not only look chemically like the central inhibitory neurotransmitter gamma-aminobutyric acid (GABA) but also act like it. The prototype gabapentin was primarily introduced to be used as antiepileptic medication. Today, both chemicals are not only utilized as adjunct antiepileptics in focal (aware and impaired awareness) seizures but are also used in several neuropathic pain conditions and other clinical indications. Their use has skyrocketed in the past few years and this has brought forward more instances of adverse effects and errors in prescribing practices. We describe here a case of a female patient with a history of diabetes, diabetic neuropathy, and hypertension being prescribed both gabapentin and pregabalin concomitantly which led to adverse effects like drowsiness, dizziness, fatigue, and ataxia. Once the patient medication profile was revisited, the pharmacy staff was able to identi...
Evidence-Based Complementary and Alternative Medicine, 2010
Canada is experiencing a growing interest in the use of alternative therapies and products partic... more Canada is experiencing a growing interest in the use of alternative therapies and products particularly natural health products (NHP). In 1997, Canadians spent around C$ 2 billion on NHP. In an attempt to catch with this popularity of NHP use, Canadian researchers and administrators from academia, industry and government jointly established the Natural Health Product Research Society of Canada (NHPRS). Since its formation, NHPRS has been organizing an annual meeting which brings together world renowned researchers and experts in the area of NHP research. For 2008, the annual NHPRS meeting took place in Toronto from the 26th to 29th of March with a focus on ‘Science Across Borders: Global Natural Health Products Research’. The scientific program was spread into three days of plenary lectures and oral presentations. The different sessions containing these talks were on: ethnobotany around the world; chemical analysis of NHP; product standards and quality control; ethnomedicine; novel ...
Glomeruli are filtering units in the kidneys. Being multicellular and complex in structure, many ... more Glomeruli are filtering units in the kidneys. Being multicellular and complex in structure, many aspects of glomerular function are yet to be elucidated. Most studies use glomerular cells in culture, which may exhibit altered physiology compared to native cells. Confocal microscopy has opened new avenues in exploring in situ glomerular function and physiology. In this report, we propose experimenting with glomerular cells in renal cortical slices and isolated intact glomeruli for Ca(2+)-handling studies. Cortical slices (100 μm thick) were obtained from mice while intact glomeruli were isolated from rats using the sieving method. These were loaded with fluo-4 and then placed in a confocal microscope. Fluo-4 was excited using a 488 nm photodiode laser and images were collected at 1 frame/sec. Changes in average fluorescence intensity (AFI) were interpreted as changes in [Ca(2+)](i). AFI increased to 37.1 ± 6.7% and 84.3 ± 20.9% with Ang II (0.01 and 0.1 μM respectively). Norepinephri...
Evidence-Based Complementary and Alternative Medicine
Background. Grewia asiatica Linn, or phalsa, is a commonly consumed fruit in Pakistan. The fruit ... more Background. Grewia asiatica Linn, or phalsa, is a commonly consumed fruit in Pakistan. The fruit is employed in the traditional medicine practice of Pakistan as a smooth muscle relaxant in different gastrointestinal (GI) and cardiovascular diseases. In this investigation, we show the antispasmodic and vasorelaxant actions of Grewia asiatica fruit extract. Methods. A 70% methanolic crude extract of the plant material was prepared (Ga.Cr). Different isolated GI tissue preparations and endothelium-intact aortas from rats were utilized to observe the pharmacological actions of the extract. Results. Ga.Cr, in increasing concentrations, inhibited the spontaneously contracting rabbit jejunum. In an effort to determine the mechanism of this relaxant action, contractions were induced in jejunum and ileum tissues with K+ (80 mM). Ga.Cr was able to only partially inhibit these induced contractions indicating that the mechanism might not be completely through a blockade of Ca2+ channels (CCB). ...
Glomeruli are filtering units in the kidneys. Being multicellular and complex in structure, many ... more Glomeruli are filtering units in the kidneys. Being multicellular and complex in structure, many aspects of glomerular function are yet to be elucidated. Most studies use glomerular cells in culture, which may exhibit altered physiology compared to native cells. Confocal microscopy has opened new avenues in exploring in situ glomerular function and physiology. In this report, we propose experimenting with glomerular cells in renal cortical slices and isolated intact glomeruli for Ca(2+)-handling studies. Cortical slices (100 μm thick) were obtained from mice while intact glomeruli were isolated from rats using the sieving method. These were loaded with fluo-4 and then placed in a confocal microscope. Fluo-4 was excited using a 488 nm photodiode laser and images were collected at 1 frame/sec. Changes in average fluorescence intensity (AFI) were interpreted as changes in [Ca(2+)](i). AFI increased to 37.1 ± 6.7% and 84.3 ± 20.9% with Ang II (0.01 and 0.1 μM respectively). Norepinephrine (10 μM), arginine vasopressin (0.1 μM) and K(+) (30 mM) also elevated AFI by 26.5 ± 6.8%, 22.3 ± 1.0% and 39.8 ± 10.3% respectively in the glomerular cells. Likewise in isolated glomeruli, Ang II (0.1-10 μM), K(+) (30-90 mM) and endothelin-1 (0.01-1 μM), all showed elevation in [Ca(2+)](i). These results give an impetus for future studies examining Ca(2+)-handling by confocal microscopy in glomerular cells using renal cortical slices and isolated intact glomeruli. The results support the utility of this system for study of glomerular physiology and pharmacology.
The hexane extract of Syzygium samarangense (Ss.Hex) dose-dependently (10D1000 μg/ ml) relaxed th... more The hexane extract of Syzygium samarangense (Ss.Hex) dose-dependently (10D1000 μg/ ml) relaxed the spontaneously contracting isolated rabbit jejunum. Four rare C-methylated flavonoids with a chalcone and a flavanone skeleton were isolated from Ss.Hex and were subsequently tested for spasmolytic activity. All flavonoids, identified as 2′-hydroxy-4′,6′- dimethoxy-3′-methylchalcone (1), 2′,4′-dihydroxy-6′-methoxy-3′,5′-dimethylchalcone (2), 2′,4′-dihydroxy-6′-methoxy-3′-methylchalcone (3), and 7-hydroxy-5-methoxy-6,8-dimethylflavanone (4), showed dose-dependent spasmolytic activity in the rabbit jejunum with IC50 values of 148.3 ± 69.4, 77.2 ± 43.5, 142.4 ± 58.6 and 178.5 ± 37.5 μg/ml (mean ± SEM), respectively. The dihydrochalcone derivative of compound 1, 2′-hydroxy-4′,6′-dimethoxy-3′- methyldihydrochalcone (5), when tested for spasmolytic activity, did not significantly relax the smooth muscle relative to the other compounds. Verapamil, a standard spasmolytic, has an IC50 value of 0...
Raphanus sativus, commonly known as radish, is a food plant known worldwide for its culinary and ... more Raphanus sativus, commonly known as radish, is a food plant known worldwide for its culinary and medicinal properties especially as a laxative and abortifacient. This study reports the gastrointestinal and uterine tone modulatory activities of the crude extract (Rl.Cr) of radish leaves. Rl.Cr, showing the presence of saponins and alkaloids, exhibited a spasmogenic effect (0.03-10 mg/mL) in isolated rabbit jejunum, rat stomach fundus and uterus which was partially blocked by atropine. In contrast, Rl.Cr was found to be devoid of any stimulatory effect in rat ileum, instead showed an inhibitory effect (0.1 mg/mL) on the ACh dose-response curves. A mild relaxant effect was also observed in rabbit jejunum at the lower doses (0.1-0.3 mg/mL) but not against K(+)-induced contractions, ruling out a calcium channel blocking effect. In guinea-pig ileum, Rl.Cr exhibited a stimulant effect resistant to atropine while sensitive to pyrilamine pretreatment. The aqueous fraction, showing a strong presence of saponins, was found to be more efficacious than the non-polar fractions in its spasmogenic effect. This study shows the presence of species-dependent gastrointestinal effects of radish mediated partially through cholinergic receptors in rabbit and rat tissues, but through histaminergic activation in the guinea-pig, providing a scientific basis for its use in gut and uterine affections while also giving a wider picture of the activity profile of radish by using different species of animals.
The effect of a crude extract of the aerial parts of Artemisia vulgaris (Av.Cr) was investigated ... more The effect of a crude extract of the aerial parts of Artemisia vulgaris (Av.Cr) was investigated against D-galactosamine (D-GalN) and lipopolysaccharide (LPS) induced hepatitis in mice. Co-administration of D-GalN (700 mg[sol ]kg) and LPS (1 microg[sol ]kg) significantly (p < 0.05) raised the plasma levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in mice in the toxin group compared with the values in the control group. Pre-treatment of mice with different doses of Av.Cr (150-600 mg[sol ]kg) significantly (p < 0.05) reduced the toxin-induced rise in plasma ALT and AST. The hepatoprotective effect was further verified by histopathology of the liver, which showed improved architecture, absence of parenchyma congestion, decreased cellular swelling and apoptotic cells, compared with the findings in the toxin group of animals. These findings scientifically validated the traditional use of Artemisia vulgaris for various liver disorders.
Gabapentinoids comprise the medications gabapentin and pregabalin. These were designed to not onl... more Gabapentinoids comprise the medications gabapentin and pregabalin. These were designed to not only look chemically like the central inhibitory neurotransmitter gamma-aminobutyric acid (GABA) but also act like it. The prototype gabapentin was primarily introduced to be used as antiepileptic medication. Today, both chemicals are not only utilized as adjunct antiepileptics in focal (aware and impaired awareness) seizures but are also used in several neuropathic pain conditions and other clinical indications. Their use has skyrocketed in the past few years and this has brought forward more instances of adverse effects and errors in prescribing practices. We describe here a case of a female patient with a history of diabetes, diabetic neuropathy, and hypertension being prescribed both gabapentin and pregabalin concomitantly which led to adverse effects like drowsiness, dizziness, fatigue, and ataxia. Once the patient medication profile was revisited, the pharmacy staff was able to identi...
Evidence-Based Complementary and Alternative Medicine, 2010
Canada is experiencing a growing interest in the use of alternative therapies and products partic... more Canada is experiencing a growing interest in the use of alternative therapies and products particularly natural health products (NHP). In 1997, Canadians spent around C$ 2 billion on NHP. In an attempt to catch with this popularity of NHP use, Canadian researchers and administrators from academia, industry and government jointly established the Natural Health Product Research Society of Canada (NHPRS). Since its formation, NHPRS has been organizing an annual meeting which brings together world renowned researchers and experts in the area of NHP research. For 2008, the annual NHPRS meeting took place in Toronto from the 26th to 29th of March with a focus on ‘Science Across Borders: Global Natural Health Products Research’. The scientific program was spread into three days of plenary lectures and oral presentations. The different sessions containing these talks were on: ethnobotany around the world; chemical analysis of NHP; product standards and quality control; ethnomedicine; novel ...
Glomeruli are filtering units in the kidneys. Being multicellular and complex in structure, many ... more Glomeruli are filtering units in the kidneys. Being multicellular and complex in structure, many aspects of glomerular function are yet to be elucidated. Most studies use glomerular cells in culture, which may exhibit altered physiology compared to native cells. Confocal microscopy has opened new avenues in exploring in situ glomerular function and physiology. In this report, we propose experimenting with glomerular cells in renal cortical slices and isolated intact glomeruli for Ca(2+)-handling studies. Cortical slices (100 μm thick) were obtained from mice while intact glomeruli were isolated from rats using the sieving method. These were loaded with fluo-4 and then placed in a confocal microscope. Fluo-4 was excited using a 488 nm photodiode laser and images were collected at 1 frame/sec. Changes in average fluorescence intensity (AFI) were interpreted as changes in [Ca(2+)](i). AFI increased to 37.1 ± 6.7% and 84.3 ± 20.9% with Ang II (0.01 and 0.1 μM respectively). Norepinephri...
Evidence-Based Complementary and Alternative Medicine
Background. Grewia asiatica Linn, or phalsa, is a commonly consumed fruit in Pakistan. The fruit ... more Background. Grewia asiatica Linn, or phalsa, is a commonly consumed fruit in Pakistan. The fruit is employed in the traditional medicine practice of Pakistan as a smooth muscle relaxant in different gastrointestinal (GI) and cardiovascular diseases. In this investigation, we show the antispasmodic and vasorelaxant actions of Grewia asiatica fruit extract. Methods. A 70% methanolic crude extract of the plant material was prepared (Ga.Cr). Different isolated GI tissue preparations and endothelium-intact aortas from rats were utilized to observe the pharmacological actions of the extract. Results. Ga.Cr, in increasing concentrations, inhibited the spontaneously contracting rabbit jejunum. In an effort to determine the mechanism of this relaxant action, contractions were induced in jejunum and ileum tissues with K+ (80 mM). Ga.Cr was able to only partially inhibit these induced contractions indicating that the mechanism might not be completely through a blockade of Ca2+ channels (CCB). ...
Glomeruli are filtering units in the kidneys. Being multicellular and complex in structure, many ... more Glomeruli are filtering units in the kidneys. Being multicellular and complex in structure, many aspects of glomerular function are yet to be elucidated. Most studies use glomerular cells in culture, which may exhibit altered physiology compared to native cells. Confocal microscopy has opened new avenues in exploring in situ glomerular function and physiology. In this report, we propose experimenting with glomerular cells in renal cortical slices and isolated intact glomeruli for Ca(2+)-handling studies. Cortical slices (100 μm thick) were obtained from mice while intact glomeruli were isolated from rats using the sieving method. These were loaded with fluo-4 and then placed in a confocal microscope. Fluo-4 was excited using a 488 nm photodiode laser and images were collected at 1 frame/sec. Changes in average fluorescence intensity (AFI) were interpreted as changes in [Ca(2+)](i). AFI increased to 37.1 ± 6.7% and 84.3 ± 20.9% with Ang II (0.01 and 0.1 μM respectively). Norepinephrine (10 μM), arginine vasopressin (0.1 μM) and K(+) (30 mM) also elevated AFI by 26.5 ± 6.8%, 22.3 ± 1.0% and 39.8 ± 10.3% respectively in the glomerular cells. Likewise in isolated glomeruli, Ang II (0.1-10 μM), K(+) (30-90 mM) and endothelin-1 (0.01-1 μM), all showed elevation in [Ca(2+)](i). These results give an impetus for future studies examining Ca(2+)-handling by confocal microscopy in glomerular cells using renal cortical slices and isolated intact glomeruli. The results support the utility of this system for study of glomerular physiology and pharmacology.
The hexane extract of Syzygium samarangense (Ss.Hex) dose-dependently (10D1000 μg/ ml) relaxed th... more The hexane extract of Syzygium samarangense (Ss.Hex) dose-dependently (10D1000 μg/ ml) relaxed the spontaneously contracting isolated rabbit jejunum. Four rare C-methylated flavonoids with a chalcone and a flavanone skeleton were isolated from Ss.Hex and were subsequently tested for spasmolytic activity. All flavonoids, identified as 2′-hydroxy-4′,6′- dimethoxy-3′-methylchalcone (1), 2′,4′-dihydroxy-6′-methoxy-3′,5′-dimethylchalcone (2), 2′,4′-dihydroxy-6′-methoxy-3′-methylchalcone (3), and 7-hydroxy-5-methoxy-6,8-dimethylflavanone (4), showed dose-dependent spasmolytic activity in the rabbit jejunum with IC50 values of 148.3 ± 69.4, 77.2 ± 43.5, 142.4 ± 58.6 and 178.5 ± 37.5 μg/ml (mean ± SEM), respectively. The dihydrochalcone derivative of compound 1, 2′-hydroxy-4′,6′-dimethoxy-3′- methyldihydrochalcone (5), when tested for spasmolytic activity, did not significantly relax the smooth muscle relative to the other compounds. Verapamil, a standard spasmolytic, has an IC50 value of 0...
Raphanus sativus, commonly known as radish, is a food plant known worldwide for its culinary and ... more Raphanus sativus, commonly known as radish, is a food plant known worldwide for its culinary and medicinal properties especially as a laxative and abortifacient. This study reports the gastrointestinal and uterine tone modulatory activities of the crude extract (Rl.Cr) of radish leaves. Rl.Cr, showing the presence of saponins and alkaloids, exhibited a spasmogenic effect (0.03-10 mg/mL) in isolated rabbit jejunum, rat stomach fundus and uterus which was partially blocked by atropine. In contrast, Rl.Cr was found to be devoid of any stimulatory effect in rat ileum, instead showed an inhibitory effect (0.1 mg/mL) on the ACh dose-response curves. A mild relaxant effect was also observed in rabbit jejunum at the lower doses (0.1-0.3 mg/mL) but not against K(+)-induced contractions, ruling out a calcium channel blocking effect. In guinea-pig ileum, Rl.Cr exhibited a stimulant effect resistant to atropine while sensitive to pyrilamine pretreatment. The aqueous fraction, showing a strong presence of saponins, was found to be more efficacious than the non-polar fractions in its spasmogenic effect. This study shows the presence of species-dependent gastrointestinal effects of radish mediated partially through cholinergic receptors in rabbit and rat tissues, but through histaminergic activation in the guinea-pig, providing a scientific basis for its use in gut and uterine affections while also giving a wider picture of the activity profile of radish by using different species of animals.
The effect of a crude extract of the aerial parts of Artemisia vulgaris (Av.Cr) was investigated ... more The effect of a crude extract of the aerial parts of Artemisia vulgaris (Av.Cr) was investigated against D-galactosamine (D-GalN) and lipopolysaccharide (LPS) induced hepatitis in mice. Co-administration of D-GalN (700 mg[sol ]kg) and LPS (1 microg[sol ]kg) significantly (p < 0.05) raised the plasma levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in mice in the toxin group compared with the values in the control group. Pre-treatment of mice with different doses of Av.Cr (150-600 mg[sol ]kg) significantly (p < 0.05) reduced the toxin-induced rise in plasma ALT and AST. The hepatoprotective effect was further verified by histopathology of the liver, which showed improved architecture, absence of parenchyma congestion, decreased cellular swelling and apoptotic cells, compared with the findings in the toxin group of animals. These findings scientifically validated the traditional use of Artemisia vulgaris for various liver disorders.
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