Preliminary report of Iranian Registry of Alzheimer's disease in Tehran province: A cross-sectional study in Iran.

Background and Aims: Alzheimer's disease (AD) is the main cause of dementia and over the 55 million people live with dementia worldwide. We aimed to establish the first database called the Iranian Alzheimer's Disease Registry to create a powerful source for future research in the country. In this report, the design and early results of the Iranian Alzheimer's Disease Registry will be described. Methods: We performed this multicenter investigation and patients' data including age, sex, educational level, disease status, Mini-Mental State Examination (MMSE), and Geriatric Depression Scale (GDS) from 2018 to 2021 were collected, registered, and analyzed by GraphPad Prism software. Results: Totally 200 AD patients were registered in our database. 107 (54%) were women and age of 147 (74%) were over 65. The mean age for men and women was 76.20 ± 8.29 and 76.40 ± 8.83 years, respectively. 132 (66%) were married and 64 (32%) were illiterate. Also, 94 (47%) were in the moderate stage of disease, and 150 (75%) lived at home together with their families. The most frequent neurological comorbidity was psychosis (n = 72, 36%), while hypertension was the most common non-neurological comorbidity (n = 104, 52%). The GDS score of women in the mild stage (5.23 ± 2.9 vs. 6.9 ± 2.6, p = 0.005) and moderate stage (5.36 ± 2.4 vs. 8.21 ± 2.06, p = <0.001) of the disease was significantly greater than men. In univariate analysis, MMSC score was remarkably associated with stroke (ß = -2.25, p = 0.03), psychosis (ß = -2.18, p = 0.009), diabetes (ß = 3.6, p = <0.001), and hypercholesteremia (ß = 1.67, p = 0.05). Also, the MMSE score showed a notable relationship with stroke (ß = -2.13, p = 0.05) and diabetes (ß = 3.26, p = <0.001) in multivariate analysis. Conclusion: Iranian Alzheimer's Disease Registry can provide epidemiological and clinical data to use for purposes such as enhancing the current AD management in clinical centers, filling the gaps in preventative care, and establishing effective monitoring and cure for the disease.

Sinomenine Attenuates Trimethyltin-Induced Cognitive Decline via Targeting Hippocampal Oxidative Stress and Neuroinflammation.

Sinomenine is the main bioactive ingredient of the medicinal plant Sinomenium acutum with neuroprotective potential. This study was designed to assess beneficial effect of sinomenine in alleviation of trimethyltin (TMT)-induced cognitive dysfunction. TMT was administered i.p. (8 mg/kg, once) and sinomenine was daily given p.o. 1 h after TMT for 3 weeks at doses of 25 or 100 mg/kg. Cognitive performance was assessed in various behavioral tests. In addition, oxidative stress- and inflammation-associated factors were measured and histochemical evaluation of the hippocampus was conducted. Sinomenine at a dose of 100 mg/kg significantly and partially increased discrimination index in novel object recognition (NOR), improved alternation in short-term Y maze, increased step-through latency in passive avoidance paradigm, and also reduced probe trial errors and latency in the Barnes maze task. Moreover, sinomenine somewhat prevented inappropriate hippocampal changes of malondialdehyde (MDA), reactive oxygen species (ROS), protein carbonyl, nitrite, superoxide dismutase (SOD), tumor necrosis factor α (TNFα), interleukin 6 (IL 6), acetylcholinesterase (AChE) activity, beta secretase 1 (BACE 1) activity, and mitochondrial membrane potential (MMP) with no significant effect on glutathione (GSH), catalase, glutathione reductase, glutathione peroxidase, and myeloperoxidase (MPO). In addition, lower reactivity (IRA) for glial fibrillary acidic protein (GFAP) as an index of astrocyte activity was observed and loss of CA1 pyramidal neurons was attenuated following sinomenine treatment. This study demonstrated that sinomenine could lessen TMT-induced cognitive dysfunction which is partly due to its attenuation of hippocampal oxidative stress and neuroinflammation.

Anti-aging Klotho Protects SH-SY5Y Cells Against Amyloid ß1-42 Neurotoxicity: Involvement of Wnt1/pCREB/Nrf2/HO-1 Signaling.

Alzheimer's disease (AD) is considered a prevalent neurological disorder with a neurodegenerative nature in elderly people. Oxidative stress and neuroinflammation due to amyloid ß (Aß) peptides are strongly involved in AD pathogenesis. Klotho is an anti-aging protein with multiple protective effects that its deficiency is involved in development of age-related disorders. In this study, we investigated the beneficial effect of Klotho pretreatment at different concentrations of 0.5, 1, and 2 nM against Aß1-42 toxicity at a concentration of 20 µM in human SH-SY5Y neuroblastoma cells. Our findings showed that Klotho could significantly and partially restore cell viability and decrease reactive oxygen species (known as ROS) and improve superoxide dismutase activity (SOD) in addition to reduction of caspase 3 activity and DNA fragmentation following Aß1-42 challenge. In addition, exogenous Klotho also reduced inflammatory biomarkers consisting of nuclear factor-kB (NF-kB), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) in Aß-exposed cells. Besides, Klotho caused downregulation of Wnt1 level, upregulation of phosphorylated cyclic AMP response element binding (pCREB), and mRNA levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) with no significant alteration of epsilon isoform of protein kinase C (PKCε) after Aß toxicity. In summary, Klotho could alleviate apoptosis, oxidative stress, and inflammation in human neuroblastoma cells after Aß challenge and its beneficial effect is partially exerted through appropriate modulation of Wnt1/pCREB/Nrf2/HO-1 signaling.

Diosgenin Attenuates Cognitive Impairment in Streptozotocin-Induced Diabetic Rats: Underlying Mechanisms.

OBJECTIVE: Prolonged diabetes mellitus causes impairments of cognition and attentional dysfunctions. Diosgenin belongs to a group of steroidal saponins with reported anti-diabetic and numerous protective properties. This research aimed to assess the effect of diosgenin on beneficially ameliorating learning and memory decline in a rat model of type 1 diabetes caused by streptozotocin (STZ) and to explore its modes of action including involvement in oxidative stress and inflammation. METHODS: Rats were assigned to one of four experimental groups, comprising control, control under treatment with diosgenin, diabetic, and diabetic under treatment with diosgenin. Diosgenin was given daily p.o. (40 mg/kg) for 5 weeks. RESULTS: The administration of diosgenin to the diabetic group reduced the deficits of functional performance in behavioral tests, consisting of Y-maze, passive avoidance, radial arm maze, and novel object discrimination tasks (recognitive). Furthermore, diosgenin treatment attenuated hippocampal acetylcholinesterase activity and malon-dialdehyde, along with improvement of antioxidants such as superoxide dismutase and glutathione. Meanwhile, the hippocampal levels of inflammatory indicators, namely interleukin 6, nuclear factor-κB, toll-like receptor 4, tumor necrosis factor α, and astrocyte-specific biomarker glial fibrillary acidic protein, were lower and, on the other hand, tissue levels of nuclear factor (erythroid-derived 2)-related factor 2 were elevated upon diosgenin administration. Besides, the mushroom-like spines of the pyramidal neurons of the hippocampal CA1 area decreased in the diabetic group, and this was alleviated following diosgenin medication. CONCLUSIONS: Taken together, diosgenin is capable of ameliorating cognitive deficits in STZ-diabetic animals, partly due to its amelioration of oxidative stress, inflammation, astrogliosis, and possibly improvement of cholinergic function in addition to its neuroprotective potential.

Sinomenine Alleviates Murine Experimental Autoimmune Encephalomyelitis Model of Multiple Sclerosis through Inhibiting NLRP3 Inflammasome.

Multiple sclerosis (MS) is known as a chronic neuroinflammatory disorder typified by an immune-mediated demyelination process with ensuing axonal damage and loss. Sinomenine is a natural alkaloid with different therapeutic benefits, including anti-inflammatory and immunosuppressive activities. In this study, possible beneficial effects of sinomenine in an MOG-induced model of MS were determined. Sinomenine was given to MOG35-55-immunized C57BL/6 mice at doses of 25 or 100 mg/kg/day after onset of MS clinical signs till day 30 post-immunization. Analyzed data showed that sinomenine reduces severity of the clinical signs and to some extent decreases tissue level of pro-inflammatory cytokines IL-1ß, IL-6, IL-18, TNFα, IL-17A, and increases level of anti-inflammatory IL-10. In addition, sinomenine successfully attenuated tissue levels of inflammasome NLRP3, ASC, and caspase 1 besides its reduction of intensity of neuroinflammation, demyelination, and axonal damage and loss in lumbar spinal cord specimens. Furthermore, immunoreactivity for MBP decreased and increased for GFAP and Iba1 after MOG-immunization, which was in part reversed upon sinomenine administration. Overall, sinomenine decreases EAE severity, which is attributed to its alleviation of microglial and astrocytic mobilization, demyelination, and axonal damage along with its suppression of neuroinflammation, and its beneficial effect is also associated with its inhibitory effects on inflammasome and pyroptotic pathways; this may be of potential benefit for the primary progressive phenotype of MS.

Ellagic acid ameliorates neuroinflammation and demyelination in experimental autoimmune encephalomyelitis: Involvement of NLRP3 and pyroptosis.

Multiple sclerosis (MS) is presented as the most common autoimmune and demyelinating neurological disorder with incapacitating complications and with no definite therapy. Most treatments for MS mainly focus on attenuation of its severity and recurrence. To model MS reliably to study pathogenesis and efficacy of possible chemicals, experimental autoimmune encephalomyelitis (EAE) condition is induced in rodents. Ellagic acid is a neuroprotective polyphenol that can protect against demyelination. This study was planned and conducted to assess its possible beneficial effect in MOG-induced EAE model of MS with emphasis on uncovering its modes of action. Ellagic acid was given p.o. (at doses of 10 or 50 mg/kg/day) after development of clinical signs of MS to C57BL/6 mice immunized with MOG35-55. Results showed that ellagic acid can ameliorate severity of the disease and partially restore tissue level of TNFα, IL-6, IL-17A and IL-10. Besides, ellagic acid lowered tissue levels of NLRP3 and caspase 1 in addition to its mitigation of neuroinflammation, demyelination and axonal damage in spinal cord specimens of EAE group. As well, ellagic acid treatment prevented reduction of MBP and decreased GFAP and Iba1 immunoreactivity. Taken together, ellagic acid can decrease severity of EAE via amelioration of astrogliosis, astrocyte activation, demyelination, neuroinflammation and axonal damage that is partly related to its effects on NLRP3 inflammasome and pyroptotic pathway.

The Association Between Circulating Klotho and Dipeptidyl Peptidase-4 Activity and Inflammatory Cytokines in Elderly Patients With Alzheimer Disease.

INTRODUCTION: Klotho and Dipeptidyl Peptidase-4 (DPP4) are two proteins that modulate inflammatory pathways. We investigated the association between circulating klotho and DPP4 activity and their relationship with inflammatory cytokines, miR-29a, and miR-195 in Alzheimer Disease (AD). METHODS: This study was conducted on 16 AD patients and 16 healthy age-matched controls. Plasma levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß, interleukin-6 (IL-6), klotho, and DPP4 were measured by enzyme-linked immunosorbent assay. Plasma expression of miR-29a and miR-195 were also measured and compared by a real-time polymerase chain reaction. RESULTS: There was a significant increase in TNF-α (p=0.006), IL-1ß (p=0.012), and IL-6 (p=0.012) levels in the AD subjects compared with controls. Also, we found a decrease in plasma levels of klotho and an increase in plasma levels of DPP4 in the AD group that was not significant compared with the controls. Lower expression of miR-29a (P=0.009) and higher expression of miR-195 (P=0.003) were observed in the AD group that was significant than controls. Further analysis showed a negative correlation between klotho and plasma levels of IL-6 (r=-0.58, p=0.01). Also, there was a positive correlation between plasma DPP4 activity and TNF-α levels (r=0.50, P=0.04) and IL-1ß (r=0.62, P=0.01). Likewise, plasma klotho concentration showed a negative correlation with the age of AD subjects (r=-0.56, P=0.02). CONCLUSION: TNF-α, IL-1ß, and IL-6 are involved in AD pathophysiology, and dysregulation of DPP4 and klotho may be associated with the inflammatory response of AD. Down-regulation of miR-29a and up-regulation of miR-195 indicated the role of miRNAs in the AD process.

Berberine ameliorates lipopolysaccharide-induced learning and memory deficit in the rat: insights into underlying molecular mechanisms.

Systemic lipopolysaccharide (LPS) triggers neuroinflammation with consequent development of behavioral and cognitive deficits. Neuroinflammation plays a crucial role in the pathogenesis of neurodegenerative disorders including Alzheimer's disease (AD). Berberine is an isoquinoline alkaloid in Berberis genus with antioxidant and anti-inflammatory property and protective effects in neurodegenerative disorders. In this research, beneficial effect of this alkaloid against LPS-induced cognitive decline was assessed in the adult male rats. LPS was intraperitoneally administered at a dose of 1 mg/kg to induce neuroinflammation and berberine was given via gavage at doses of 10 or 50 mg/kg, one h after LPS, for 7 days. Treatment of LPS group with berberine at a dose of 50 mg/kg (but not at a dose of 10 mg/kg) improved spatial recognition memory in Y maze, performance in novel object recognition task (NORT), and prevented learning and memory dysfunction in passive avoidance tasks. Furthermore, berberine lowered hippocampal activity of acetylcholinesterase (AChE), malondialdehyde (MDA), protein carbonyl, activity of caspase 3, and DNA fragmentation and improved antioxidant capacity through enhancing glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase, and glutathione (GSH). Besides, berberine attenuated inflammation-related indices, as was evident by lower levels of nuclear factor-kappa B (NF-κB), toll-like receptor 4 (TLR4), tumor necrosis factor α (TNFα), and interleukin 6 (IL-6). Berberine also appropriately restored hippocampal 3-nitrotyrosine (3-NT), cyclooxygenase 2 (Cox 2), glial fibrillary acidic protein (GFAP), sirtuin 1, and mitogen-activated protein kinase (p38 MAPK) with no significant alteration of brain-derived neurotrophic factor (BDNF). In summary, berberine could partially ameliorate LPS-induced cognitive deficits via partial suppression of apoptotic cascade, neuroinflammation, oxido-nitrosative stress, AChE, MAPK, and restoration of sirtuin 1.

Naringenin ameliorates learning and memory impairment following systemic lipopolysaccharide challenge in the rat.

Systemic inflammation following infection is usually associated with long-term complications including cognitive deficit and dementia. Neuroinflammation and cognitive decline are also main hallmarks of several neurological conditions. Naringenin is a citrus flavanone with anti-inflammatory, neuroprotective, and antioxidant potential. In this study, the protective effect of naringenin against lipopolysaccharide (LPS)-induced cognitive decline was evaluated in the rat. LPS was daily injected at a dose of 167 µg/kg for 1 week and naringenin was administered p.o. at doses of 25, 50, or 100 mg/kg/day. Treatment of LPS-injected rats with naringenin dose-dependently improved spatial recognition memory in Y maze, discrimination ratio in novel object discrimination task, and retention and recall capability in passive avoidance test. Furthermore, naringenin lowered hippocampal malondialdehyde (MDA) as an index of lipid peroxidation and improved antioxidant defensive system comprising superoxide dismutase (SOD), catalase, and glutathione (GSH) in addition to decreasing acetylcholinesterase (AChE) activity. Additionally, naringenin was able to lower hippocampal nuclear factor-kappaB (NF-κB), toll-like receptor 4 (TLR4), tumor necrosis factor α (TNFα), cyclooxygenase-2 (COX2), inducible nitric oxide synthase (iNOS), glial fibrillary acidic protein (GFAP) level and its immunoreactivity, and to elevate nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Taken together, naringenin could alleviate LPS-induced cognitive deficits and neuroinflammation, as was evident from attenuation of oxidative stress and AChE and modulation of Nrf2/NF-κB/TNFα/COX2/iNOS/TLR4/GFAP.

Ellagic acid ameliorates learning and memory deficits in a rat model of Alzheimer's disease: an exploration of underlying mechanisms.

RATIONALE: Alzheimer's disease (AD) is a neurodegenerative disorder with irreversible loss of intellectual abilities. Current therapies for AD are still insufficient. OBJECTIVE: In this study, the effect of ellagic acid on learning and memory deficits was evaluated in intrahippocampal amyloid beta (Aß25-35)-microinjected rats and its modes of action were also explored. METHODS: AD rat model was induced by bilateral intrahippocampal microinjection of Aß25-35 and ellagic acid was daily administered (10, 50, and 100 mg/kg), and learning, recognition memory, and spatial memory were evaluated in addition to histochemical assessment, oxidative stress, cholinesterases activity, and level of nuclear factor-kappaB (NF-κB), Toll-like receptor 4 (TLR4), and nuclear factor (erythroid-derived 2)-like 2 (Nrf2). RESULTS: The amyloid beta-microinjected rats showed a lower discrimination ratio in novel object and alternation score in Y maze tasks and exhibited an impairment of retention and recall capability in passive avoidance paradigm and higher working and reference memory errors in radial arm maze (RAM). In addition, amyloid beta group showed a lower number of Nissl-stained neurons in CA1 area in addition to enhanced oxidative stress, higher activity of cholinesterases, greater level of NF-κB and TLR4, and lower level of nuclear/cytoplasmic ratio for Nrf2 and ellagic acid at a dose of 100 mg/kg significantly prevented most of these abnormal alterations. CONCLUSIONS: Ellagic acid pretreatment of intrahippocampal amyloid beta-microinjected rats could dose-dependently improve learning and memory deficits via neuronal protection and at molecular level through mitigation of oxidative stress and acetylcholinesterase (AChE) activity and modulation of NF-κB/Nrf2/TLR4 signaling pathway.

Acetyl-l-carnitine protects dopaminergic nigrostriatal pathway in 6-hydroxydopamine-induced model of Parkinson's disease in the rat.

Parkinson's disease (PD) is a movement disorder and the second most common neurodegenerative disease worldwide in which nigrostriatal dopaminergic neurons within substantia nigra pars compacta (SNC) are lost, with clinical motor and non-motor symptoms including bradykinesia, resting tremor, rigidity, stooping posture and cognitive deficits. This study was undertaken to evaluate the neuroprotective potential of acetyl-l-carnitine (ALC) against unilateral striatal 6-hydroxydopamine (6-OHDA)-induced model of PD and to explore some involved mechanisms. In this experimental study, intrastriatal 6-OHDA-lesioned rats received ALC at doses of 100 or 200mg/kg/day for 1 week. ALC (200mg/kg) lowered apomorphine-induced rotational asymmetry and reduced the latency to initiate and the total time in the narrow beam test, reduced striatal malondialdehyde (MDA), increased catalase activity and glutathione (GSH) level, prevented reduction of nigral tyrosine hydroxylase (TH)-positive neurons and striatal TH-immunoreactivity, and lowered striatal glial fibrillary acidic protein (GFAP) and its immunoreactivity as an indicator of astrogliosis, and nuclear factor NF-kappa B and Toll-like receptor 4 (TLR4) as reliable markers of neuroinflammation. Meanwhile, ALC at both doses mitigated nigral DNA fragmentation as a valuable marker of apoptosis. The results of this study clearly suggest the neuroprotective effect of ALC in 6-OHDA-induced model of PD through abrogation of neuroinflammation, apoptosis, astrogliosis, and oxidative stress and it may be put forward as an ancillary therapeutic candidate for controlling PD.

Berberine ameliorates intrahippocampal kainate-induced status epilepticus and consequent epileptogenic process in the rat: Underlying mechanisms.

Status epilepticus (SE) is a life-threatening neurologic condition, instigating epileptogenesis to transform normal brain to an epileptic condition. SE is followed by spontaneous recurrent seizures (SRS) and final development of temporal lobe epilepsy (TLE) that is resistant to treatment. Neuroprotective strategies are increasingly put forward as a promising therapy to prevent and/or manage epileptic conditions. In this study, we investigated whether berberis alkaloid, i.e. berberine (BBR), could ameliorate intrahippocampal kainate-induced SE and its consequent epileptogenic process and to explore some underlying mechanisms. BBR was daily administered at doses of 25 or 50mg/kg. Results showed that BBR treatment of kainate-microinjected rats at a dose of 50mg/kg lowered the incidence of SE and SRS. It also significantly restored hippocampal level of reactive oxygen species (ROS), glutathione (GSH), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), activity of catalase and caspase 3, nuclear factor-B (NF-κB), toll-like receptor 4 (TLR4), tumor necrosis factor α (TNFα), interleukin-1ß (IL-1ß), neural cell adhesion molecule (NCAM), glial fibrillary acidic protein (GFAP), cathepsin D, and heme oxygenase 1 (HO-1). Additionally, BBR protected against hippocampal CA3 neuronal loss and prevented development of aberrant mossy fiber sprouting (MFS) as an essential element of chronic epileptogenic circuit. These data suggest that BBR could mitigate SE and SRS in intrahippocampal kainate model of epilepsy and exert neuroprotective effect and its influence is mainly mediated via suppression of oxidative stress, neuroinflammation, and possibly apoptosis.

Garlic active constituent s-allyl cysteine protects against lipopolysaccharide-induced cognitive deficits in the rat: Possible involved mechanisms.

Neuroinflammation is known as a risk factor for cognitive deficit and dementia and its incidence increases with aging. S-allyl cysteine (SAC) is the active and main component of aged garlic extract with anti-inflammatory, neuroprotective, and nootropic potential. In this study, the protective effect of SAC against lipopolysaccharide (LPS)-induced cognitive deficit in the rat was investigated. For induction of learning and memory impairment and neuroinflammation, LPS was intraperitoneally injected at a dose of 167µg/kg for 7 days and SAC was administered p.o. at doses of 25, 50, or 100mg/kg/day, 30min after LPS, for seven days. Treatment of LPS-injected rats with SAC at a dose of 100mg/kg improved spatial recognition memory in Y maze, discrimination ratio in novel object discrimination task, and retention and recall in passive avoidance test. In addition, SAC at the latter dose mitigated lipid peroxidation marker malondialdehyde (MDA) and augmented key antioxidant defensive elements including superoxide dismutase (SOD), catalase and glutathione (GSH) in hippocampal homogenate and lowered acetylcholinesterase activity. Meanwhile, SAC down-regulated hippocampal nuclear factor-B, toll-like receptor 4 (TLR4), glial fibrillary acidic protein (GFAP), and interleukin 1ß (IL-1ß) and up-regulated nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in addition to lowering iba1-immunoreactive intensity in the hippocampus of LPS-injected group. Taken together, SAC administration could mitigate LPS-induced cognitive deficits via attenuation of oxidative stress, neuroinflammation, astrogliosis, and acetylcholinesterase activity.

S-allyl cysteine ameliorates cognitive deficits in streptozotocin-diabetic rats via suppression of oxidative stress, inflammation, and acetylcholinesterase.

Diabetes mellitus (DM) is associated with learning, memory, and cognitive deficits. S-allyl cysteine (SAC) is the main organosulfur bioactive molecule in aged garlic extract with anti-diabetic, antioxidant, anti-inflammatory and nootropic property. This research was conducted to evaluate the efficacy of SAC on alleviation of learning and memory deficits in streptozotocin (STZ)-diabetic rats and to explore involvement of toll-like receptor 4 (TLR4), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), nuclear factor-kappa B (NF-κB), and heme oxygenase 1 (HO-1) signaling cascade. Male Wistar rats were divided into control, diabetic, SAC-treated diabetic, and glibenclamide-treated diabetic (positive control) groups. SAC was administered at a dose of 150mg/kg for seven weeks. Treatment of diabetic rats with SAC lowered serum glucose, improved spatial recognition memory in Y maze, discrimination ratio in novel object recognition task, and restored step-through latency (STL) in passive avoidance paradigm. In addition, SAC reduced acetylcholinesterase activity, lipid peroxidation marker malondialdehyde (MDA) and augmented antioxidant defensive system including superoxide dismutase (SOD), catalase and reduced glutathione (GSH) in hippocampal lysate. Meanwhile, SAC lowered hippocampal NF-kB, TLR4, and TNFα and prevented reduction of Nrf2 and heme oxygenase-1 (HO-1) in diabetic rats. Taken together, chronic SAC treatment could ameliorate cognitive deficits in STZ-diabetic rats through modulation of Nrf2/NF-κB/TLR4/HO-1, and acetylcholinesterase and attenuation of associated oxidative stress and neuroinflammation.

Carnosine exerts neuroprotective effect against 6-hydroxydopamine toxicity in hemiparkinsonian rat.

Parkinson's disease (PD) is the second most common disorder of the central nervous system due to the degeneration of mesencephalic dopaminergic neurons. Current treatments for PD have a symptomatic relief strategy with no prevention of disease progression. Due to the neuroprotective and antiapoptotic potential of the natural dipeptide carnosine, this study was conducted to assess its beneficial effect in 6-hydroxydopamine (6-OHDA)-induced model of PD in rat. Unilateral intrastriatal 6-OHDA-lesioned rats received i.p. carnosine at a dose of 250 mg/kg twice at an interval of 24 h, which started presurgery. Apomorphine caused contralateral rotations, a significant reduction in the number of Nissl-stained neurons on the left side of the substantia nigra, and increased apoptosis was observed with enhanced oxidative stress burden in 6-OHDA-lesioned rats. Carnosine pretreatment significantly reduced rotations, attenuated apoptosis, and restored malondialdehyde and nitrite content and catalase activity with no significant effect on reduced glutathione (GSH). These results indicate that prelesion administration of carnosine could exert neuroprotection against 6-OHDA toxicity, and this may be of benefit in patients with early PD.

Rhino-orbitocerebral mucormycosis in a patient with idiopathic crescentic glomerulonephritis.

Mucormycosis, caused by mucorales, is an acute, rapidly progressive infection associated with high mortality. Rhino-orbitocerebral infection is the most common variant and is generally seen in association with immune deficiency syndromes. Prompt medical treatment of this infection and debridement decreases the mortality rate. We describe a 47-year-old man with crescentic glomerulonephritis on maintenance prednisolone therapy. He had earlier received steroid and cyclophosphamide pulse therapies. Renal functions improved following immunosuppressive treatment. In the third month of maintenance therapy, he presented to us with left-sided facial swelling and bloody nasal discharge. He had high blood sugar and acidic blood pH (ketoacidosis), probably due to steroid therapy. Magnetic resonance imaging of the head and sinuses showed inflammation and mass in the ethmoid sinus and nose with partial septal destruction, proptosis, global destruction of the left eye, brain infarction and carotid artery obliteration. Endoscopic biopsy of the sinuses revealed severe tissue necrosis. Samples of nasal discharge and biopsy tissue showed aseptate hyphae on light microscopy and culture, compatible with Rhizopus. The patient was treated with amphotericin B and multiple wound debridements along with ethmoidectomy and enucleation of the left eye. He was discharged in good general condition but with mild right hemiparesis. On follow-up examination at one year, there were no signs of fungal infection or renal dysfunction.

Impact of psychological problems in chemical warfare survivors with severe ophthalmologic complication, a cross sectional study.

BACKGROUND: Sulfur mustard (SM) has been used as a chemical warfare agent since the early twentieth century. Despite the large number of studies that have investigated SM induced ocular injuries, few of those studies have also focused on the psychological health status of victims. This study has evaluated the most prominent influences on the psychological health status of patients with severe SM induced ocular injuries. METHODS: This descriptive study was conducted on 149 Iranian war veterans with severe SM induced eye injuries. The psychological health status of all patients was assessed using the Iranian standardized Symptom Check List 90-Revised (SCL90-R) questionnaire. The results of patients' Global Severity Index (GSI) were compared with the optimal cut-off point of 0.4 that has previously been calculated for GSI in Iranian community. The Mann-Whitney U test, T tests and effect sizes (using Cohen's d) were employed as statistical methods. Data were analyzed using SPSS software. RESULTS: The mean age of patients was 44.86 (SD=8.7) and mean duration of disease was 21.58 (SD=1.20) years. Rate of exposure was once in 99 (66.4%) cases. The mean GSI (1.46) of the study group was higher compared to standardized cut off point (0.4) of the Iranian community. The results of this study showed that the mean of total GSI score was higher in participants with lower educational levels (effect size=0.507), unemployment (effect size=0.464) and having more than 3 children (effect size=0.62). Among the participants, 87 (58.4%) cases had a positive psychological history for hospitalization or receiving outpatient cares previously and 62 (41.6%) cases had a negative psychological history. In addition, the mean of GSI in participants with negative psychological history was lower than those with positive psychological history (Mean Change Difference=-0.621 with SD=0.120). There was a significant difference between positive and negative psychological history with respect to GSI (P<0.001). CONCLUSION: The study showed that severe ophthalmologic complications in chemical survivors are accompanied with destructive effects on psychological health status. Appropriate management may improve psychological health status in these patients.