Beneficial impact of Nesfatin-1 on reproductive dysfunction induced by nicotine in male rats: Possible modulation of autophagy and pyroptosis signaling pathways.

This study was conducted to explore the beneficial impact of nesfatin-1 on reproductive dysfunction induced by nicotine (NT) in male rats with possible modulation of autophagy and pyroptosis signaling pathways. This research was performed on 40 Wistar male rats. They were distributed into four groups: control, normal+nesfatin-1, NT, and NT+nesfatin-1. At the end of the experimental period, the serum was separated for assay of testosterone, FSH and LH. Also, sperm parameters were determined. Histopathological examination of testicular tissue and immunohistochemical analysis was done for mammalian target of rapamycin, AMP-activated protein kinase, and mitogen-activated protein kinases including phosphorylated extracellular signal regulated kinase and phosphorylated cJun N-terminal kinase. Relative gene expression was determined for testicular nucleotide oligomerization domain (NOD)-like receptors proteins and Caspase-1, and autophagy markers including microtubule-associated protein 1 light chain 3 alpha and Beclin-1. Also, the following testicular parameters were assayed: 3ß-hydroxysteroid dehydrogenase, 17ß-hydroxysteroid dehydrogenase, malondialdehyde, superoxide dismutase activity, catalase, glucose-6 phosphate dehydrogenase, reactive oxygen species, caspase-3 activity, IL-1ß, IL-18, mitochondrial transmembrane potential and Complex-I activity. The results revealed that the normal+nesfatin-1 group showed insignificant changes as compared to the control group. Meanwhile, the NT group exhibited prominent reproductive dysfunction in male rats. On the other hand, in the NT+nesfatin-1 group nesfatin-1 notably attenuated this reproductive dysfunction as evidenced by improvement of hormonal assay, sperm parameters, histopathological picture, immunohistochemical evaluation and real time relative gene expressions. In conclusion: Nesfatin-1 alleviated the impairment of male reproductive functions induced by NT via enhancement of autophagy pathways, suppression of pyroptosis, apoptosis, mitochondrial dysfunction and ROS production. Thus nesfatin-1 may offer a novel protective or therapeutic access for treating male infertility.

The possible role of heat shock protein-70 induction in collagen-induced arthritis in rats.

AIM: This study aimed to evaluate the possible role of heat shock protein-70 (HSP70) induction by 17-allylaminodemethoxygeldanamycin (17-AAG) in collagen-induced arthritis in rats. MATERIAL AND METHODS: Male Wistar rats were divided into five groups (n = 10/group) and were treated intraperitoneally twice a week for 4 weeks, namely normal control (saline), arthritis control (AR; saline), AR + 17-AAG, AR + methotrexate (MTX), and AR + 17-AAG + MTX. At the end of the treatments, arthritic score was determined and then the animals were sacrificed. Erythrocyte sedimentation rate (ESR), serum levels of HSP70, interleukin-17 (IL-17), tumor necrosis factor-alpha (TNF-α), rheumatic factor (RF), C-reactive protein (CRP), malondialdehyde (MDA), glutathione peroxidase (GPx), and matrix metalloproteinase-9 (MMP-9) were determined. RESULTS: In the AR group, all parameters increased significantly, except for GPx, which showed a pronounced decrease. The 17-AAG and/or MTX treatments significantly reduced arthritic score, ESR, IL-17, TNF-α, RF, CRP, MDA, and MMP-9 with significant increase in GPx compared to the AR group. The HSP70 level was significantly higher in the AR + 17-AAG and the AR + 17-AAG + MTX groups but significantly lower in the AR + MTX group as compared to the AR group. Also, it was significantly lower in the AR + MTX group as compared to the AR + 17-AAG group. CONCLUSION: We concluded that HSP70 induction by 17-AAG attenuated the inflammatory process in a rheumatoid arthritis (RA) model induced by collagen, which suggested that HSP70 inducers can be promising agents in the treatment of RA.

Oral valgancyclovir versus intravenous gancyclovir for cytomegalovirus prophylaxis in kidney transplant recipients.

BACKGROUND: Prophylaxis against cytomegalovirus (CMV) is a regular practice in organ transplantation. Oral valgancyclovir appears to be an interesting alternative to the usual intravenous form. PATIENTS AND METHODS: We prospectively compared the response of intravenous gancyclovir for 2 weeks (GAN; n=41) to oral valgancyclovir for 2 weeks (VAL2w; n=23) or 3 months (VAL3m; n=46) in kidney transplant recipients receiving induction immunosuppression. CMV antigenemia assay and/or polymerase chain reaction (PCR) were used for viral detection. Patients were followed for a minimum of 6 months posttransplantation. SPSS software was used for statistical analysis using a cutoff of significance as P<.05. RESULTS: There was no statistical difference in the demographic features among the study groups. However, human leukocyte antigen (HLA) match was better in the VAL3m group and the patients of this group received less ATG induction immunosuppression (41.3%) compared with the GAN group (100%). The incidence of acute rejection was not different among the study groups. There was a higher incidence of fever with positive CMV tests in the VAL2w group (P=.035) compared with the other groups, while leukopenia with a negative CMV test was significantly higher in the VAL3m group (P=.04). The incidence of CMV disease was higher in the VAL2w group (30.4%) compared with the GAN group (14.6%) or the VAL3m group (8.7%). Renal function was significantly worse in the VAL2w group at 3 and 6 months (P=.011 and .02, respectively). CONCLUSIONS: Three months oral valgancyclovir prophylaxis for CMV was a more effective regimen compared with intravenous gancyclovir for 2 weeks. Shorter courses were associated with a higher incidence of CMV infection and poorer graft function. Leukopenia observed in patients receiving valgancyclovir may be a drug-related side effect.

[Synthetic meshes for transvaginal surgical cure of genital prolapse: evaluation in 2005]. / Les prothèses synthétiques dans la cure de prolapsus génitaux par la voie vaginale: bilan en 2005.

Since 1996, prosthetic meshes have become increasingly popular for transvaginal surgical cure of genital prolapse. In light of the growing number of proposed techniques and materials we reviewed the experience of the pioneers in order to provide surgeons with the most objective information available. We reviewed the literature indexed in Meline/PubMed and Current Contents retaining all work concerning resorbable and non-resorbable meshes. For the larger class of non-resorbable meshes we also reviewed articles by category of material, each type of mesh being carefully defined: different compositions of polypropylene, polyester, composite meshes and also insertion kits. Resorbable meshes were evaluated in two randomized studies which did not demonstrate better results than with simple folding known to have a high rate of recurrence. For polypropylene meshes, Marlex was studied in six trials which demonstrated a high rate of cure at one year but also a high rate of erosion which reached 25%. Use of Atrium was mentioned in three studies with a 6 to 12% recurrence rate and an erosion rate nearly reaching 20%. The majority of studies used Prolene and Gynemesh. Seventeen authors reported their experience, generally reviewing retrospective series, with recurrence rates of less than 10% for follow-up periods rarely greater than two years. A large variety of forms and sizes have been used, hindering comparisons. The rate of erosion was also quite variable, as high as 45%, demonstrating the need for a precise definition of erosion. Only recently have authors shown interest in the impact of prosthetic meshes on quality of life and sexual activity. An improvement is generally noted for defecation but the rate of dyspareunia has reached as high as 60%. Here again grades of prosthetic retraction should be better defined. Proposed to improve these phenomena, soft Prolene recently used by several authors does not appear to fulfil expectations. Since 2005, several precut polypropylene meshes have been proposed with an insertion kit. The Prolift kit has been followed prospectively in 100 patients undergoing regular surveillance. Surgipro has been used sporadically in small series but follow-up is still too short for proper assessment. Polyester meshes (Mersilene and Paritex) have been presented by three authors who have found them useful but reports have been vague concerning results and complications. Polytetrafluoroethylene has not been evaluated for transvaginal surgery, probably because of the poor tolerance of suburetral bands. For composite meshes, Vypro has been used by four authors who noted about 10% erosion but with a short follow-up insufficient to draw conclusions about the functional and anatomic outcome. Surfaced meshes, advocated for transvaginal treatments, have been studied in only two reports. Plevitex is a polypropylene mesh coated with collagen; another polyester composite with polyglactin 910. The rate of dyspareunia varied from 14 to 24%. Other composites with antiadherents or antiseptics are also proposed for transvaginal insertion but have not been studied. This work demonstrated the lack of sufficient evidence from prospective randomized trials and the lack of standardized techniques to draw any definite conclusions. While evidence is being accumulated on the lower rate of recurrence for anterior compartment prolapse, the lack of data on the rate of complications and patient quality of life is unacceptable for this functional surgery. We still have reservations about widespread use of synthetic meshes. A special chapter is detailed in appendix on post-operative complications. These new specific complications call to a new semiology, with a classification in 4 types and under-types, proposed by authors. Type 1: defects of healing. Type 2: the infection of the graft. Type 3: the shrinkage of the mesh. Type 4: erosions. Authors detail the symptoms of these 4 types as well as the prevention and the treatment of these complications.

Clinical Utility of Viral Load in the Management of Cytomegalovirus Infection in Solid Organ Transplant Patients in Kuwait.

BACKGROUND: Infection with human cytomegalovirus (CMV) in solid organ transplant patients remains an unresolved challenge, despite improvements in immunosuppressive therapy, post-transplantation care, viral prevention, and therapy. METHODS: We conducted quantitative real-time polymerase chain reaction (PCR) assays of CMV on plasma samples of 1,168 patients in Kuwait who received solid organ transplants from 2012 to 2014 to detect and monitor CMV DNA viral load. RESULTS: Of the 1,168 patients, 180 (15.4%) were positive for CMV DNA. Among the CMV DNA-positive patients, 119 (66.1%) remained without symptoms and 61 (33.9%) developed CMV-related symptoms. During the follow-up period, peak viral loads were significantly (P < .05) higher in symptomatic patients (mean 970 copies/mL; range, 15-625,000 copies/mL) than in asymptomatic patients (<150 copies/mL; range, 67-2,650 copies/mL). Many symptomatic patients (n = 57) were successfully treated, and their viral loads declined. However, some symptomatic patients had irregular viral-load kinetics, with prolonged periods of symptoms despite CMV treatment; we excluded the possibility of drug resistance in these patients, because there was no evidence of clinical resistance to treatment. CONCLUSIONS: Quantitative real-time PCR of CMV DNA is useful in monitoring CMV infection and the effectiveness of CMV treatment in renal transplant recipients in Kuwait.

Restoration of mycobacterial antigen-induced proliferation and interferon-gamma responses in peripheral blood mononuclear cells of tuberculosis patients upon effective chemotherapy.

Peripheral blood mononuclear cells (PBMC) were obtained from culture-proven tuberculosis (TB) patients before and after 2 and 6 months of chemotherapy with a multi-drug regimen. PBMC were tested for cellular responses in antigen-induced proliferation and interferon-gamma (IFN-gamma) assays in response to complex mycobacterial antigens (whole cell Mycobacterium bovis BCG and M. tuberculosis, cell walls and short-term culture filtrate [ST-CF] of M. tuberculosis), fractionated ST-CF antigens (fractions F1-F10) and ESAT-6. The responses in TB patients before anti-TB treatment were low (median stimulation index (SI)=1-7, median delta IFN-gamma=0-12 U ml(-1), and percent responders=13-67%) to all the antigenic preparations. Following the administration of anti-TB chemotherapy for 2 months, there were significant (P<0.05) improvements in the cellular responses (median SI=9-76, median delta IFN-gamma=3-70 U ml(-1), and percent responders=33-100%) to most of the antigenic preparations tested. However, concanavalin A-induced proliferation responses of PBMC from the same patients before and after 2 months of chemotherapy were high and comparable (median SI=101 and 114, respectively, P>0.05, 100% responders). A further increase in IFN-gamma responses (median delta IFN-gamma=14-250 U ml(-1) and percent responders=43-100%) to mycobacterial antigens was observed in patients receiving chemotherapy for 6 months. Among the ST-CF fractions, F1 and F2 containing low molecular mass proteins resulted in the highest responses, whereas ESAT-6 showed responses comparable to these fractions only in a minority of the patients. HLA-DR typing of these patients showed heterogeneity in the expression of molecules encoded by HLA-DRB genes. These results show that effective chemotherapy restores cellular responses of TB patients to a large number of M. tuberculosis antigens, which could be useful in monitoring the efficacy of anti-TB treatment.

Nigella sativa oil, nigellone and derived thymoquinone inhibit synthesis of 5-lipoxygenase products in polymorphonuclear leukocytes from rats.

In the present study, Nigella sativa oil (NSO), nigellone (polythymoquinone) and derived thymoquinone were studied to evaluate their effect on the formation of 5-lipoxygenase (5-LO) products from polymorphonuclear leukocytes (PMNL).NSO produced a concentration dependent inhibition of 5-LO products and 5-hydroxy-eicosa-tetra-enoic acid (5-HETE) production with half maximal effects (IC(50)) at 25+/-1 micro g/ml, respectively 24+/-1 micro g/ml. Nigellone caused a concentration-related inhibition of 5-HETE production (IC(50): 11.9+/-0.3 micro g/ml). Moreover thymoquinone, the active principle of NSO inhibited the production of 5-LO products (IC(50): 0.26+/-0.02 micro g/ml) and 5-HETE production (IC(50): 0.36+/-0.02 micro g/ml) in a similar way. The effects are probably due to an antioxidative action. The data may in part explain the effect of the oil, its derived thymoquinone and nigellone in ameliorating inflammatory diseases.

[Circulatory and respiratory effects of ketamine in horses anesthetized with halothane]. / Effets circulatoires et respiratoires de la kétamine chez le cheval anesthésié à l'halothane.

Ketamine (0.3 mg/kg) administered intravenously to 12 halothane anesthetized horses caused a significant respiratory depression during ten minutes when respiration was spontaneous. Significant hemodynamic effects were not observed except for cardiac index. Clinical application was also discussed.

[Study of two goitrous endemic areas in Niger: Belley-Koira and Tiguey-Tallawal]. / Etude de deux foyers d'endémie goitreuse au Niger: Belley-Koira et Tiguey-Tallawal.

The present work reports the clinical and laboratory findings in two endemic areas in Niger: Tiguey-Tallawal and Belley-Koira. The goitrous subjects (n = 293), mainly children and adolescents, have clinical evidence of euthyroidism but with biological criteria of hypothyroidism in 25% of cases as shown by the decrease of the total serum T4 and the increase of serum TSH. Iodine deficiency intake evaluated by the determination of urinary iodine in single urine specimens is the permissive and main factor for goiter endemicity = 14 +/- 7 micrograms/l in Belley-Koira (n = 99), 26 +/- 23 micrograms/l in Tiguey (n = 155) and 25 +/- 19 micrograms/l in Tallawal (n = 95). The single intramuscular injection of iodized oil (240 mg of iodine) constitutes an extremely effective way of correcting iodine deficiency: decrease of volume or disappearance of goiter among 291 subjects out of 362 i.e. 80%, twelve months after the injection. The diffuse goiter, more numerous (n = 270) than nodular goiter (n = 92) are corrected with more efficiency (85% versus 50%). We also noted that non goitrous subjects living in these two endemic areas show a severe iodine deficiency (urinary iodine: 33 +/- 18 mu/l; n = 70 = 76) while those living in non endemic areas present a moderate or a low iodine deficiency, respectively in Niamey (urinary iodine: 48 +/- 36 micrograms/l; n = 200) and in Tamou (urinary iodine: 80 +/- 29 micrograms/l; n = 69). Severe, moderate and low iodine deficiency seem to be correlated with nutritional habits: mil in endemic areas, mil and meat in Niamey and mil, meat, milk and fish in Tamou. The nutriments eaten in Niger have a low iodine level except ewe milk: salt (270 to 7100 micrograms/kg), woman milk (40 +/- 21 micrograms/l) cow milk (22 micrograms/l) goat milk (50 micrograms/l), ewe milk (294 micrograms/l). Salt consumption, evaluated by the determination of urinary chloride, is adequate. Prophylaxis by iodinated salt should be well accepted. No other factors than iodine deficiency in the etiology of endemic goiter, mainly nutritional (goitrogens or protein-calorie malnutrition) can be evoked to explain clinical and biochemical discrepancies between subjects living in the same morbid territory.

Avian anesthesia.

Providing a safe anesthetic environment is the key to successful avian anesthesia. Knowledge and understanding the anatomic and physiologic differences between birds and mammals help to prevent most emergency situations and guide responses in critical situations. Thorough preanesthetic history and examination, correction of underlying conditions, and use of simple anesthetic protocols all optimize the outcome of the procedure. Finally, critical monitoring helps to anticipate most crises and reduces incidences of mortality and morbidity in avian anesthesia.

Comparison of in vitro tests for evaluation of passive transfer of immunoglobulins in giraffe (Giraffa camelopardalis).

Serum samples from captive giraffe (Giraffa camelopardalis) were tested to assess passive transfer of immunoglobulins using in vitro methods developed for domestic ruminants. Estimated immunoglobulin levels were compared using five tests (protein electrophoresis, total protein refractometry, zinc sulfate turbidity, glutaraldehyde coagulation, and sodium sulfite turbidity). A linear relationship was observed among total protein, gamma globulin (electrophoretic measurement), and immunoglobulin level based on spectrophotometric measurement of zinc sulfate turbidity. Nonquantitative assays also demonstrated statistical correlation with the quantitative methods. Using criteria similar to those established for domestic species, cutoff values for failure of passive transfer (FPT) were established for these tests in neonatal giraffe: 1) total protein <6.0 g/dl; 2) gamma globulin < 0.5 g/dl; 3) estimated immunoglobulin level < 1,000 mg/dl (zinc sulfate turbidity); 4) glutaraldehyde coagulation test negative; or 5) no visually detectable turbidity in 16% sodium sulfite or Bova-S negative. Retrospective examination of the medical histories showed a strong statistical association between animals designated as having FPT and those that were removed from their dams based on clinical assessment to be hand-reared. Application of these tests in the field should allow earlier detection and intervention for FPT in neonatal giraffe.

Sarcocystis neurona-like encephalitis in a Canada lynx (Felis lynx canadensis).

A 13-yr-old female Canada lynx (Felis lynx canadensis) died after a short clinical illness, and necropsy revealed multifocal, nonsuppurative encephalitis with protozoal schizonts present in cerebral vascular endothelial cells. The schizonts stained immunohistochemically with antiserum to Sarcocystis neurona. This is the first report of Sarcocystis encephalitis in the Canada lynx.

Surgical technique for intra-abdominal radiotransmitter placement in North American river otters (Lontra canadensis).

Twenty-two free-ranging North American river otters (Lontra canadensis) from northern and eastern New York were captured and surgically implanted with radiotransmitters as part of a relocation project. The surgical technique involved an incision in the paralumbar fossa and transection through the abdominal musculature to introduce a radiotransmitter into the abdominal cavity. Two complications were encountered. Excessive hemorrhage occurred during one procedure. The otter was treated for blood loss with fluids, and it recovered uneventfully. Surgical incision infection occurred in a second animal. The otter was treated with metronidazole and enrofloxacin, and the wound was cleaned daily with chlorhexidine. The otter recovered uneventfully. Otters were released in western New York state. Postrelease monitoring via radiotelemetry revealed that the otters became established in their new ranges. The intra-abdominal implants did not affect their survival or reproductive potential.

Cytomegalovirus genotypes gB1 and gH1 are the most predominant genotypes among renal transplant recipients in Kuwait.

BACKGROUND: The human cytomegalovirus (HCMV) is a common pathogen responsible for asymptomatic and persistent infections in healthy individuals. However, cytomegalovirus infections are a major cause of morbidity and mortality in immunocompromised patients, especially in recipients of solid-organ transplants and AIDS patients. METHODS: HCMV DNA from 42 patients who received kidney transplants between 2004 and 2008 were subjected to polymerase chain reaction and restriction fragment length polymorphism to identify HCMV gB and gH genotypes. RESULTS: HCMV gB1 and gH1 genotypes were the most the predominant HCMV genotypes (P < .05, P < .05, respectively). In addition, both HCMV gB1 and gH1 genotype were significantly more often associated with the development of fever with leukopenia and severe HCMV disease than other gB or gH2 genotypes. No significant differences were observed among viral loads between the HCMV genotypes among infected individuals. CONCLUSION: This study demonstrated the prevalence and role of HCMV genotypes in infection and disease in renal transplant patients in Kuwait.

[Cryoglobulinemia type II]. / Cryoglobulinémie de type II.

Cryoglobulinemia type II is a disease characterized by the presence of a monoclonal rheumatoid factor (mostly IgM) and by widespread deposition of immune aggregates that contain the monoclonal IgM RF. Complement and its receptor on erythrocytes, by transporting immune complexes in the circulation, are particularly adapted to protect the organism against immune deposition. This physiological system does not function appropriately in the presence of a monoclonal RF that depletes complement proteins, enhances immune aggregation and inhibits opsonization of circulating immune complexes. However many other factors are involved in the failure of normal clearance of immune complexes in this disease (excessive load of immune complexes, defective Fc-mediated clearance reactions, etc.) all of which concur to provide the most favorable conditions for the deposition of immune aggregates, or for the trapping of circulating immune complexes at the site of ongoing immune injury.

Abnormal immune adherence and elimination of hepatitis B surface antigen/antibody complexes in patients with AIDS.

C3b-coated immune complexes (IC) adhere to complement receptor 1 (CR1) on human E in the circulation. E from AIDS patients have an acquired low CR1 number. To study immune adherence and IC elimination in AIDS, radiolabeled hepatitis B surface Ag/antibody complexes were injected i.v. in six AIDS patients and in 14 healthy controls. The binding of IC to E was reduced in AIDS patients (mean binding 2 min after injection: 24.9 +/- 13.3%) compared with healthy individuals (63 +/- 3.7%) (p = 0.0005). The low binding correlated directly with the number of CR1/E and to the capacity of these E to bind IC in vitro. During the first 15 min disappearance of IC was faster in AIDS patients than in normal subjects and correlated with CR1 number. Thereafter, elimination was very slow in AIDS patients, which suggested that a fraction of IC might be released back into the circulation similarly to what has been observed for C3b-coated E. When the data were analyzed with a mathematical model allowing for such release to occur, five of six AIDS patients had a high release rate compared with little or no release in normal individuals (p less than 0.001). Thus, low CR1 on E is responsible for defective immune adherence, and might determine abnormal disappearance of IC from the circulation as well.

Intensive Psychiatric Rehabilitation Treatment (IPRT): an overview of a new program.

Intensive Psychiatric Rehabilitation Treatment (IPRT) is a new program of out-patient psychiatric rehabilitation which is currently operating in New York State and Iowa. IPRT is based upon a process of psychiatric rehabilitation which was developed at the Boston University Center for Psychiatric Rehabilitation. The purpose of IPRT is to assist individuals with serious and persistent mental illness in identifying and achieving personally meaningful goals within the community. This article will provide an overview of IPRT by examining the program as it operates in New York State, the research foundations of the program, and the preliminary results of a state-wide evaluation of IPRT programs. IPRT is an important new program of outpatient psychiatric rehabilitation. Controlled studies are needed to establish the effectiveness of the program.

Immune adherence and clearance of hepatitis B surface Ag/Ab complexes is abnormal in patients with systemic lupus erythematosus (SLE).

Complement levels and complement receptor 1 (CR1) on erythrocytes (E) are reduced in systemic lupus erythematosus (SLE). To see whether these abnormalities are responsible for defective transport and elimination of immune complexes (IC) from the circulation, patients with active SLE (14) and normal volunteers (14) were injected with preformed IC (hepatitis B surface Ag/Ab). Two minutes after injection only 25.9 +/- 19.1% (mean +/- 1 s.d.) of the circulating IC were bound to E in the SLE patients as compared to 63 +/- 3.7% in the normal subjects (P = 0.0001). For SLE patients, the reduced immune adherence was best explained by a combination of complement depletion and low CR1 binding capacity (tau = 0.80, P = 0.0001). The disappearance of IC as estimated from the area under the elimination curve was faster in SLE than in controls (P = 0.02), and correlated with CR1 (tau = 0.54, P = 0.0001) and immune adherence observed in vivo (tau = 0.33, P = 0.013). Finally, immune adherence was absent and IC disappeared very rapidly in a patient with C2 deficiency and an SLE-like disease. These observations suggest that in SLE the defective immune adherence reaction might be responsible for the accelerated disappearance of IC from the circulation.

Defective immune adherence and elimination of hepatitis B surface antigen/antibody complexes in patients with mixed essential cryoglobulinemia type II.

Mixed essential cryoglobulinemia type II (monoclonal Ig/polyclonal IgG) is characterized by systemic vasculitis caused by the deposition of circulating immune reactants that include the monoclonal component. Such reactants may include immune complexes (IC) formed from exogenous Ag. IC binding to E C receptor type 1 appears to play a role in transport and buffering of such IC (immune adherence: IA). To define the mechanisms responsible for immune deposition, 7 patients with cryoglobulinemia type II (IgM kappa/polyclonal IgG) and 14 normal volunteers were injected i.v. with hepatitis B surface Ag/antibody complexes. Two minutes after injection, only 19.4% (mean) of the circulating complexes were bound to E in patients as compared with 63.1% in normal subjects. This IA correlated directly with C4 and inversely with the IgM rheumatoid factor (RF) titer. Disappearance of IC was faster in patients (mean elimination rate: 15.7%/min) than in normal subjects (9.3%). In vitro experiments demonstrated that C depletion, interference with IC opsonization by monoclonal IgM RF, and decreased binding of opsonized IC in the presence of monoclonal RF are each associated with decreased IA. These observations suggest that, in patients with cryoglobulinemia type II, monoclonal IgM RF and low C contribute to reducing IA of circulating IC that might be rapidly trapped in tissues, resulting in injury.

Immune adherence of nascent hepatitis B surface antigen-antibody complexes in vivo in humans.

Upon i.v. injection into humans, pre-formed immune complexes bind complement and adhere to complement receptor type I (CR1, CD35) on erythrocytes (immune adherence). However, in most circumstances antigen and antibody react in the presence of complement; such nascent immune complexes may have properties different from pre-formed immune complexes. To define whether nascent immune complexes would also adhere to erythrocytes in vivo in humans, we studied immune complexes that formed upon i.v. injection of radiolabelled hepatitis B surface antigen (HBsAg) into immunized volunteers (eight subjects with anti-HBsAb levels ranging from undetectable to 50 U/ml.; and three control non-immune individuals). Immune complexes formed immediately in the subjects with detectable levels of specific antibody, and the clearance rate of these immune complexes correlated with the anti-HBsAb level (r = 0.78, P < 0.01). A fraction of the circulating immune complexes bound to erythrocytes in the three individuals with the highest antibody level (8-15% at 10 min). The effect of CR1 number per erythrocytes was analysed in two subjects with similar antibody levels and immune complexes clearance rates: immune adherence was higher in the subject with more CR1 per erythrocytes. The same immune complexes model studied in vitro provided similar results: a fraction of nascent immune complexes bound to human erythrocytes; this immune adherence was observed only when immune complexes formed in the presence of antibody excess, and correlated with CR1 number per erythrocytes (r = 0.99, P < 0.01). Finally, adherence of nascent HBsAg-antibody immune complexes to platelets was demonstrated in rabbits. Although immune adherence involves only a small fraction of nascent immune complexes at any given time, it may be essential for the safe disposal of large nascent immune complexes.