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101.
Household contacts of hepatitis C virus (HCV)-positive patients are considered at increased risk of HCV infection. This cross-sectional study during April through June 1999 assessed the prevalence and risk behaviours associated with HCV seropositivity among the household contacts of HCV seropositive thalassaemic children in Karachi, Pakistan. Among the 341 household contacts of 86 thalassaemic HCV seropositive children who were tested, 70 (20.5%) were positive for anti-HCV antibodies. The stratified analysis showed that HCV seroprevalence among the contacts did not differ significantly by the gender of the index patient and the type of relationship of contact with the index patient. However, HCV seroprevalences among the fathers and mothers of male index patients was substantially higher compared to those of female index patients. HCV RNA was recovered and genotyped from nine index patients and corresponding nine HCV-seropositive household contacts. HCV genotype 3a and 3b were found in 89% (8/9) and 11% (1/9) of the pairs, respectively. The final multivariable conditional logistic regression model revealed that after adjusting for the effect of ethnicity and past hospital admission history, the HCV-seropositive household contacts were more likely than HCV seronegative household contacts to have been bitten by the carrier [adjusted matched odds ratio (mOR)=2.6, 95% CI 1.3–5.2] or have shared a toothbrush with the carrier (adjusted mOR=8.2; 95% CI 1.56–43.5). Control efforts should focus on the risk behaviours. 相似文献
102.
Management of bleeding in haemophiliacs with a history of inhibitor remains problematic. With infusion of factor VIII (FVIII), development of an anamnestic response and possible appearance of high-titre inhibitor remains a valid concern. We report a case of a haemophiliac with a history of moderately high-titre FVIII inhibitor that had become undetectable. He had not received FVIII since 1997, when he became inhibitor negative. He had been managed during his bleeding episodes with prothrombin complex factor concentrates, which became less effective in controlling his bleeding. The patient had a history of recurrent, spontaneous shoulder joint dislocations with bleeding, pain and significant disability. Shoulder joint replacement surgery was suggested. Replacement therapy was discussed with the patient, who refused treatment with human FVIII because of his concern for possible anamnestic response and inhibitor rebound. Porcine FVIII was not acceptable due to his poor response when used once in the past, and his history of moderate allergic reaction. Therefore, recombinant factor VIIa (NovoSeven, Novo Nordisk, Princeton, NJ) was considered to be an acceptable option for the contemplated shoulder surgery. The patient underwent 2.5 h of surgery with NovoSeven infusion. The surgeons were impressed with the lack of bleeding in this traumatic surgery. Despite the continuously prolonged activated partial thromboplastin time and low FVIII levels, the patient maintained a remarkably dry surgical field. Effective haemostasis was achieved during and after this procedure. This case illustrates the usage of NovoSeven as an effective treatment modality in a haemophilia A patient with past history of inhibitor undergoing joint surgery. 相似文献
103.
Suzhao Li C. Preston Neff Kristina Barber Jaewoo Hong Yuchun Luo Tania Azam Brent E. Palmer Mayumi Fujita Cecilia Garlanda Alberto Mantovani Soohyun Kim Charles Anthony Dinarello 《Proceedings of the National Academy of Sciences of the United States of America》2015,112(8):2497-2502
Similar to IL-1α and IL-33, IL-1 family member IL-37b translocates to the nucleus and is associated with suppression of innate and adaptive immunity. Here we demonstrate an extracellular function of the IL-37 precursor and a processed form. Recombinant IL-37 precursor reduced LPS-induced IL-6 by 50% (P < 0.001) in highly inflammatory human blood-derived M1 differentiated macrophages derived from selective subjects but not M2 macrophages. In contrast, a neutralizing monoclonal anti–IL-37 increased LPS-induced IL-6, TNFα and IL-1β (P < 0.01). The suppression by IL-37 was consistently observed at low picomolar but not nanomolar concentrations. Whereas LPS induced a 12-fold increase in TNFα mRNA, IL-37 pretreatment decreased the expression to only 3-fold over background (P < 0.01). Mechanistically, LPS-induced p38 and pERK were reduced by IL-37. Recombinant IL-37 bound to the immobilized ligand binding α-chain of the IL-18 receptor as well as to the decoy receptor IL-1R8. In M1 macrophages, LPS increased the surface expression of IL-1R8. Compared with human blood monocytes, resting M1 cells express more surface IL-1R8 as well as total IL-1R8; there was a 16-fold increase in IL-1R8 mRNA levels when pretreated with IL-37. IL-37 reduced LPS-induced TNFα and IL-6 by 50–55% in mouse bone marrow-derived dendritic cells, but not in dendritic cells derived from IL-1R8–deficient mice. In mice subjected to systemic LPS-induced inflammation, pretreatment with IL-37 reduced circulating and organ cytokine levels. Thus, in addition to a nuclear function, IL-37 acts as an extracellular cytokine by binding to the IL-18 receptor but using the IL-1R8 for its anti-inflammatory properties.IL-37, previously known as IL-1 family member 7, broadly reduces innate inflammation as well as acquired immune responses (1). In human peripheral blood mononuclear cells (PBMCs), a knockdown of endogenous IL-37 results in increased production of LPS- as well as IL-1β–induced cytokines (2). Mice transgenic for full-length human IL-37 (IL-37tg) are protected against LPS-induced systemic inflammation (2), chemical colitis (3), metabolic syndrome (4), and acute myocardial infarction (5). IL-37tg mice also have suppressed immune responses following challenge by specific antigen (6). We believe that full-length IL-37 expressed in the transgenic mice is processed extracellularly.In mouse macrophages stably transfected with human IL-37, ∼20% of IL-37 translocates to the nucleus (7), which is associated with decreased cytokine production (2, 7). However, in the presence of a caspase-1 inhibitor, there is no translocation to the nucleus and no reduction in LPS-induced cytokines (7). Mutation of aspartic acid at the caspase-1 cleavage position 20 to alanine also results in failure to translocate to the nucleus and loss of the suppression of cytokine production (8). Thus, as with IL-1α and IL-33, IL-37 is the third member of the IL-1 family that translocates to the nucleus and affects cellular responses. Nevertheless, it remains unclear whether the reduction in cytokines in vitro or in vivo is due solely to nuclear translocation of IL-37.Support for an extracellular function for IL-37 comes from early studies reported over 10 y ago that demonstrated binding of IL-37 to the α-chain of IL-18 receptor (IL-18Rα). We therefore hypothesized that extracellular IL-37 can function through the IL-18Rα surface receptor to mediate its anti-inflammatory effects but that a negative or decoy receptor would be required. The candidate decoy receptor would likely be IL-1R8 [formerly, single IgG IL-1–related receptor (SIGIRR)] because, similar to IL-18BP, IL-1R8 has only a single Ig domain and is known for providing a brake on inflammation (9). In the present study, we have characterized the function of full-length recombinant IL-37b in inhibiting inflammation in vitro and in vivo and the role of IL-1R8. 相似文献
104.
105.
Jamil AZ Iqbal K Gondal TM Iqbal W Fawad-ur-Rahman Mirza KA 《Journal of the College of Physicians and Surgeons--Pakistan : JCPSP》2012,22(7):464-465
We report a case of bilateral loss of pupillary light reflex and accommodation following 360° peripheral retinal laser therapy. A 24 years old male underwent prophylactic laser barrage for peripheral retinal lattice degenerations. Soon after the procedure, he developed bilateral loss of pupillary light reflex and accommodation. The patient faced difficulty while doing near work. On instillation of 0.125% pilocarpine, both pupils demonstrated the phenomenon of denervation supersensitivity. Damage to the short ciliary nerves was the most likely mechanism responsible for this adverse outcome. 相似文献
106.
Yasin MM Nasreen G Rathore FA Malik SA 《Journal of the College of Physicians and Surgeons--Pakistan : JCPSP》2012,22(7):455-457
A 62-year-old diabetic bed ridden woman, presented to the emergency department with symptoms suggestive of peritonitis. She had been taking oral laxatives and enemas to relieve her chronic constipation for last 6 years. Hard impacted stools and pelvic tenderness were found on digital rectal examination. Her X-ray abdomen showed soft tissue shadows in the colon but there was no gas under the diaphragm on chest X-ray. Sonography found free fluid in pelvis. She was resuscitated, and her hyperglycemia was controlled by use of regular insulin as per sliding scale. Operative findings revealed free fluid in pelvis and very hard faecalomas lying free in peritoneal cavity. There was a 2 x 3 cm perforation at the anterior wall of the recto-sigmoid junction. Peritoneal toilet was carried out followed by Hartmann's procedure. Histopathology of perforation side showed no evidence of malignancy. 相似文献
107.
108.
Shargh VH Jaafari MR Khamesipour A Jaafari I Jalali SA Abbasi A Badiee A 《Vaccine》2012,30(26):3957-3964
First generation Leishmania vaccines consisting of whole killed parasites with or without adjuvants have reached phase 3 trial and failed to show enough efficacy mainly due to the lack of an appropriate adjuvant. In this study, the nuclease-resistant phosphorothioate CpG oligodeoxynucleotides (PS CpG) or nuclease-sensitive phosphodiester CpG ODNs (PO CpG) were used as adjuvants to enhance immunogenicity and rate of protection against leishmaniasis. Due to the susceptibility of PO CpG to nuclease degradation, an efficient liposomal delivery system was developed to protect them from degradation. 1, 2-dioleoyl-3-trimethylammonium-propane (DOTAP) as a cationic lipid was used because of its unique adjuvanticity and electrostatic interaction with negatively charged CpG ODNs. To evaluate the role of liposomal formulation in protection rate and enhanced immune response, BALB/c mice were immunized subcutaneously with liposomal soluble Leishmania antigens (SLA) co-incorporated with PO CpG (Lip-SLA-PO CpG), Lip-SLA-PS CpG, SLA+PO CpG, SLA+PS CpG, SLA or buffer. As criteria for protection, footpad swelling at the site of challenge, parasite loads, the levels of IFN-γ and IL-4, and the IgG subtypes were evaluated. The groups of mice receiving Lip-SLA-PO CpG or Lip-SLA-PS CpG showed a high protection rate compared with the control groups. In addition, there was no significant difference in immune response generation between mice immunized with PS CpG and the group receiving PO CpG when incorporated into the liposomes. The results suggested that liposomal form of PO CpG might be used instead of PS CpG in future vaccine formulations as an efficient adjuvant. 相似文献
109.
110.
Azam Almasi Mohammad Zarei Safoura Raoufi Abdolrahman Sarihi Iraj Salehi Alireza Komaki Nasrin Hashemi-Firouzi Siamak Shahidi 《Metabolic brain disease》2018,33(6):1859-1867
The neurotransmitter γ-aminobutyric acid (GABA) is involved in the process of memory. It has been reported that the inhibition of GABAB receptors has beneficial effects on cognition. The aim of this study was to investigate the role of CGP35348 (a GABAB receptor antagonist) on dentate gyrus GABAB receptor inhibition and its effects on learning and memory impairments that had been induced in adult male rats by microinjection of β-amyloid (Aβ). Seventy Wistar male rats were randomly divided into seven groups: control, sham (receiving the Aβ vehicle only), Aβ, Aβ + CGP35348 (1, 10, and 100 μg/μL), and CGP35348 alone (10 μg/μL). Memory impairment was induced by unilateral interventricular microinjection of Aβ (6 μg/6 μL). Rats were cannulated bilaterally in the dentate gyrus, and then, they were treated for 20 consecutive days. Learning and memory were assessed using the novel object recognition and passive avoidance learning tests. The discrimination index and the step-through latency were significantly increased in the Aβ + CGP35348 group in comparison to the Aβ only group (P?<?0.05 and P?<?0.01, respectively). Data showed that the discrimination index was decreased in the Aβ + CGP35348 group in comparison with the control group (P?<?0.05) and sham group (P?<?0.01). Moreover, the step-through latency was significantly decreased in the Aβ + CGP35348 group in comparison to the control and sham groups (P?<?0.01). Data from this study indicated that intra-hippocampal microinjection of the GABAB receptor antagonist counteracts the learning, memory, and cognitive impairments induced by Aβ. It can be concluded that the GABAB receptor antagonist is a possible therapeutic agent against the progression of acute Aβ toxicity-induced memory impairment. 相似文献