Brain derived neurotropic factors (BDNF) can be secreted either as a pro-BDNF or a mature form (m... more Brain derived neurotropic factors (BDNF) can be secreted either as a pro-BDNF or a mature form (mBDNF) through γ-amino-butyric acid (GABAA) receptors activation. Depolarization of GABA neurons in spinal cord can be mediated through N-methyl-D-aspartate (NMDA) receptor due to the exogenous secretion of over expressed BDNF. This over expressed BDNF further modulate the excitation and sensitization of nociceptors. We investigated the modulation of BDNF by GABAA agonist i.e., gabapentin, indomethacin (non-steroidal anti-inflammatory) and their low-dose combination on adjuvant-induced inflammatory arthritis. Mycobacterium tuberculosis H37Ra strain, as adjuvant, was injected in the tail base of female Sprague-Dawley rats. Gabapentin (5 mg/kg), indomethacin (5 mg/kg) and low dose combination of gabapentin (1.5 mg/kg) + indomethacin (2.5 mg/kg) were used. Paw edema was measure by plethysmometer and chronic pain was measured by plantar apparatus. Nitric oxide, peroxide and superoxide dismuta...
The global prevalence of dementia including Alzheimer’s disease (AD) is estimated to reach 44 mil... more The global prevalence of dementia including Alzheimer’s disease (AD) is estimated to reach 44 million people. AD is the most common neurodegenerative disorder described by the presence of extracellular amyloid plaques, intracellular hyperphosphorylated tau protein and neuronal loss as main hall marks of the disease. Clinically AD is recognized by the failure of memory and cognitive decline that become severe with the progression of the disease. While most of the cases of AD are sporadic and occurs over the age of 65 years, the disease may also develop in autosomal dominant familial manner and affects the relatively young population. The disease begins due to increased level of oxidative stress which is a hallmark of aging and affects many cellular processes at macromolecular level including alteration of lipids, proteins and DNA by peroxidation, oxidation and methylation. AD may also involve changes in the expression of proteases, contributes to the non-amyloidogenic and amyloidogen...
Several honey samples of Pakistani origin have been analysed for their effect on nociception. Amo... more Several honey samples of Pakistani origin have been analysed for their effect on nociception. Among the tested samples, Acacia honey showed most effective dose-dependent antinociceptive activity which was significantly different from the untreated group in tail-flick and paw-withdrawal tests (p < 0.01 and p < 0.003), respectively. The antinociceptive activity of honey reached a maximum at 60 min post-treatment and then gradually decreased, whereas the activity of indomethacin was persistent at 120 min post-treatment. The absence of antinociceptive activity in simulated honey (which contained fructose, glucose, maltose and sucrose representing the major constituents of honey) indicated that the active principle(s) might be present in minor constituents of honey.
Gait analysis in the adjuvant-induced arthritic rat model of chronic pain was used to examine the... more Gait analysis in the adjuvant-induced arthritic rat model of chronic pain was used to examine the role of GABA(A) receptors in the development of pain. Drug solutions were administered continuously at 5+/-0.75 microl/h for 14 days via Alzet osmotic pumps (2ML2) placed under the skin of the back. The GABA(A) receptor agonist, muscimol, produces a dose-dependent reversal of the gait deficits seen in arthritic rats without reducing the tibiotarsal joints inflammatory edema or the histological picture of joint erosion and inflammation. The higher infusion rate for muscimol, 20 microg/h, caused the gait for the arthritic rats to be indistinguishable from that of normal non-arthritic rats. In normal, non-arthritic rats, muscimol did not show any effect on gait. The GABA(A) receptor antagonist bicuculline showed small but significant exacerbation of stride length (P < 0.05) single and double stance time (P < 0.05) and swing time deficits (P < 0.05) in the arthritic rats, but no changes in measures of gait in the normal control rat. The results suggest that the development of arthritic pain is increased in the absence of GABA(A) receptor tone and that increasing GABA(A) receptor tone can reduce arthritic pain but does not affect the disease process.
The aim of this study was to investigate whether gait changes occurring during the development of... more The aim of this study was to investigate whether gait changes occurring during the development of carrageenan induced rodent paw inflammation could be measured to provide an objective marker of persistent pain. The objectives were to measure hind limb tibiotarsal joint diameter as an indication of inflammatory oedema and to analyse gait during the development of the carrageenan induced persistent pain. Rear paw intraplantar injection of 6 mg (150 microl) lambda-carrageenan resulted in significant swelling of rear limbs at 90 min (P=0.002). Analysis of gait, using video recordings of spontaneous animal ambulations demonstrated significant changes in gait over a 90-min period. These were primarily changes in temporal measures of gait and consisted of a reduction in velocity (P=0.005) and stride length (P=0.006) and increase in dual stance time (P=0.009). It is hypothesised that the temporal and spatial changes in gait observed in this model of acute inflammatory hyperalgesia may have been due to avoidance of the normally non-noxious mechanical stimulation induced by walking. It is suggested that gait analysis may be a suitable method for measuring early behavioural change associated with inflammatory hyperalgesia.
Shark cartilage extracts were examined for induction of cytokines and chemokines in human periphe... more Shark cartilage extracts were examined for induction of cytokines and chemokines in human peripheral blood leukocytes. Primary leukocyte cultures were exposed to a variety of aqueous and organic extracts prepared from several commercial brands of shark cartilage. From all commercial sources of shark cartilage tested the acid extracts induced higher levels of TNFalpha than other extracts. Different commercial brands of shark cartilage varied significantly in cytokine-inducing activity. TNFalpha induction was seen as early as 4 h and IFNgamma at detectable levels for up to four days. Shark cartilage extracts did not induce physiologically significant levels of IL-4. Results suggest that shark cartilage, preferentially, induces Th1 type inflammatory cytokines. When compared to bovine cartilage extract, collagen, and chondroitin sulfate, shark cartilage induced significantly higher levels of TNFalpha. Treatment with digestive proteases (trypsin and chymotrypsin) reduced the cytokine induction response by 80%, suggesting that the active component(s) in cartilage extracts is proteinaceous. The induction of Th1 type cytokine response in leukocytes is a significant finding since shark cartilage, taken as a dietary supplement for a variety of chronic degenerative diseases, would be contraindicated in cases where the underlying pathology of the chronic condition is caused by inflammation.
Oxidative stress has been reported to contribute to aging and cataract formation in the lens. The... more Oxidative stress has been reported to contribute to aging and cataract formation in the lens. The aim was to determine the association of oxidative stress with advanced glycation end products (AGEs) in elderly diabetic and non-diabetic patients with cataract. In the present study, malondialdehyde, vitamin E, serum AGEs, and glycemic control were investigated. The study included 156 subjects. Out of them, 30 were normal elderly subjects, 31 were elderly diabetic patients without cataract, 33 were elderly diabetic patients with cataract, 32 were elderly non-diabetic with cataract, and 30 were normal young subjects. The patients were selected on clinical grounds from Eye Ward, Jinnah Postgraduate Medical Centre, Karachi, Pakistan. Positive significant correlation was observed between s-AGEs and malondialdehyde in elderly diabetic and non-diabetic patients with cataract. Negative significant correlation was observed between s-AGEs and vitamin E in elderly diabetic and non-diabetic patients with cataract. However, the malondialdehyde and serum AGEs were found to be significantly increased (p < 0.001) in elderly diabetic and non-diabetic patients with and without cataract compared with elderly control subjects. In contrast to all four senile groups, the serum AGEs was significantly lower (p < 0.001) in young control subjects. Serum vitamin E was found to be significantly decreased (p < 0.001) in elderly diabetic patients with and without cataract compared with elderly control subjects. Fasting blood glucose, HbA(1C) and serum fructosamine levels were significantly increased (p < 0.001) in elderly diabetic patients with and without cataract compared with non-diabetic elderly patients with cataract and elderly control subjects. This study revealed that increased AGEs were associated with oxidative stress in the elderly groups. AGE, as a result of oxidative stress, might have a role in cataract formation, which, in diabetic patients, occurs vigorously as compared with non-diabetic cataract patients.
Brain derived neurotropic factors (BDNF) can be secreted either as a pro-BDNF or a mature form (m... more Brain derived neurotropic factors (BDNF) can be secreted either as a pro-BDNF or a mature form (mBDNF) through γ-amino-butyric acid (GABAA) receptors activation. Depolarization of GABA neurons in spinal cord can be mediated through N-methyl-D-aspartate (NMDA) receptor due to the exogenous secretion of over expressed BDNF. This over expressed BDNF further modulate the excitation and sensitization of nociceptors. We investigated the modulation of BDNF by GABAA agonist i.e., gabapentin, indomethacin (non-steroidal anti-inflammatory) and their low-dose combination on adjuvant-induced inflammatory arthritis. Mycobacterium tuberculosis H37Ra strain, as adjuvant, was injected in the tail base of female Sprague-Dawley rats. Gabapentin (5 mg/kg), indomethacin (5 mg/kg) and low dose combination of gabapentin (1.5 mg/kg) + indomethacin (2.5 mg/kg) were used. Paw edema was measure by plethysmometer and chronic pain was measured by plantar apparatus. Nitric oxide, peroxide and superoxide dismuta...
The global prevalence of dementia including Alzheimer’s disease (AD) is estimated to reach 44 mil... more The global prevalence of dementia including Alzheimer’s disease (AD) is estimated to reach 44 million people. AD is the most common neurodegenerative disorder described by the presence of extracellular amyloid plaques, intracellular hyperphosphorylated tau protein and neuronal loss as main hall marks of the disease. Clinically AD is recognized by the failure of memory and cognitive decline that become severe with the progression of the disease. While most of the cases of AD are sporadic and occurs over the age of 65 years, the disease may also develop in autosomal dominant familial manner and affects the relatively young population. The disease begins due to increased level of oxidative stress which is a hallmark of aging and affects many cellular processes at macromolecular level including alteration of lipids, proteins and DNA by peroxidation, oxidation and methylation. AD may also involve changes in the expression of proteases, contributes to the non-amyloidogenic and amyloidogen...
Several honey samples of Pakistani origin have been analysed for their effect on nociception. Amo... more Several honey samples of Pakistani origin have been analysed for their effect on nociception. Among the tested samples, Acacia honey showed most effective dose-dependent antinociceptive activity which was significantly different from the untreated group in tail-flick and paw-withdrawal tests (p < 0.01 and p < 0.003), respectively. The antinociceptive activity of honey reached a maximum at 60 min post-treatment and then gradually decreased, whereas the activity of indomethacin was persistent at 120 min post-treatment. The absence of antinociceptive activity in simulated honey (which contained fructose, glucose, maltose and sucrose representing the major constituents of honey) indicated that the active principle(s) might be present in minor constituents of honey.
Gait analysis in the adjuvant-induced arthritic rat model of chronic pain was used to examine the... more Gait analysis in the adjuvant-induced arthritic rat model of chronic pain was used to examine the role of GABA(A) receptors in the development of pain. Drug solutions were administered continuously at 5+/-0.75 microl/h for 14 days via Alzet osmotic pumps (2ML2) placed under the skin of the back. The GABA(A) receptor agonist, muscimol, produces a dose-dependent reversal of the gait deficits seen in arthritic rats without reducing the tibiotarsal joints inflammatory edema or the histological picture of joint erosion and inflammation. The higher infusion rate for muscimol, 20 microg/h, caused the gait for the arthritic rats to be indistinguishable from that of normal non-arthritic rats. In normal, non-arthritic rats, muscimol did not show any effect on gait. The GABA(A) receptor antagonist bicuculline showed small but significant exacerbation of stride length (P < 0.05) single and double stance time (P < 0.05) and swing time deficits (P < 0.05) in the arthritic rats, but no changes in measures of gait in the normal control rat. The results suggest that the development of arthritic pain is increased in the absence of GABA(A) receptor tone and that increasing GABA(A) receptor tone can reduce arthritic pain but does not affect the disease process.
The aim of this study was to investigate whether gait changes occurring during the development of... more The aim of this study was to investigate whether gait changes occurring during the development of carrageenan induced rodent paw inflammation could be measured to provide an objective marker of persistent pain. The objectives were to measure hind limb tibiotarsal joint diameter as an indication of inflammatory oedema and to analyse gait during the development of the carrageenan induced persistent pain. Rear paw intraplantar injection of 6 mg (150 microl) lambda-carrageenan resulted in significant swelling of rear limbs at 90 min (P=0.002). Analysis of gait, using video recordings of spontaneous animal ambulations demonstrated significant changes in gait over a 90-min period. These were primarily changes in temporal measures of gait and consisted of a reduction in velocity (P=0.005) and stride length (P=0.006) and increase in dual stance time (P=0.009). It is hypothesised that the temporal and spatial changes in gait observed in this model of acute inflammatory hyperalgesia may have been due to avoidance of the normally non-noxious mechanical stimulation induced by walking. It is suggested that gait analysis may be a suitable method for measuring early behavioural change associated with inflammatory hyperalgesia.
Shark cartilage extracts were examined for induction of cytokines and chemokines in human periphe... more Shark cartilage extracts were examined for induction of cytokines and chemokines in human peripheral blood leukocytes. Primary leukocyte cultures were exposed to a variety of aqueous and organic extracts prepared from several commercial brands of shark cartilage. From all commercial sources of shark cartilage tested the acid extracts induced higher levels of TNFalpha than other extracts. Different commercial brands of shark cartilage varied significantly in cytokine-inducing activity. TNFalpha induction was seen as early as 4 h and IFNgamma at detectable levels for up to four days. Shark cartilage extracts did not induce physiologically significant levels of IL-4. Results suggest that shark cartilage, preferentially, induces Th1 type inflammatory cytokines. When compared to bovine cartilage extract, collagen, and chondroitin sulfate, shark cartilage induced significantly higher levels of TNFalpha. Treatment with digestive proteases (trypsin and chymotrypsin) reduced the cytokine induction response by 80%, suggesting that the active component(s) in cartilage extracts is proteinaceous. The induction of Th1 type cytokine response in leukocytes is a significant finding since shark cartilage, taken as a dietary supplement for a variety of chronic degenerative diseases, would be contraindicated in cases where the underlying pathology of the chronic condition is caused by inflammation.
Oxidative stress has been reported to contribute to aging and cataract formation in the lens. The... more Oxidative stress has been reported to contribute to aging and cataract formation in the lens. The aim was to determine the association of oxidative stress with advanced glycation end products (AGEs) in elderly diabetic and non-diabetic patients with cataract. In the present study, malondialdehyde, vitamin E, serum AGEs, and glycemic control were investigated. The study included 156 subjects. Out of them, 30 were normal elderly subjects, 31 were elderly diabetic patients without cataract, 33 were elderly diabetic patients with cataract, 32 were elderly non-diabetic with cataract, and 30 were normal young subjects. The patients were selected on clinical grounds from Eye Ward, Jinnah Postgraduate Medical Centre, Karachi, Pakistan. Positive significant correlation was observed between s-AGEs and malondialdehyde in elderly diabetic and non-diabetic patients with cataract. Negative significant correlation was observed between s-AGEs and vitamin E in elderly diabetic and non-diabetic patients with cataract. However, the malondialdehyde and serum AGEs were found to be significantly increased (p < 0.001) in elderly diabetic and non-diabetic patients with and without cataract compared with elderly control subjects. In contrast to all four senile groups, the serum AGEs was significantly lower (p < 0.001) in young control subjects. Serum vitamin E was found to be significantly decreased (p < 0.001) in elderly diabetic patients with and without cataract compared with elderly control subjects. Fasting blood glucose, HbA(1C) and serum fructosamine levels were significantly increased (p < 0.001) in elderly diabetic patients with and without cataract compared with non-diabetic elderly patients with cataract and elderly control subjects. This study revealed that increased AGEs were associated with oxidative stress in the elderly groups. AGE, as a result of oxidative stress, might have a role in cataract formation, which, in diabetic patients, occurs vigorously as compared with non-diabetic cataract patients.
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Papers by Dr Shabana U. Simjee