GRP78 levels, regional fat distribution and endometrial cáncer / Niveles de GRP78, distribución regional del tejido adiposo y cáncer endometrial

Background: The association of obesity with endometrial cancer is supported by the presence of endoplasmic reticulum (ER) stress in the adipocyte. Glucose-regulated protein 78 (GRP78) is a marker for ER stress. This protein is a central regulator of ER stress due to its major anti-apoptotic role. It plays an important role in tumor development, progression and chemoresistance. Aim: To look for an association between android and gynoid obesity, plasma GRP78 levels and endometrial cancer. Material and methods: Forty four patients with endometrial cancer aged 72 ± 6 years and 44 healthy women aged 55 ± 9 years were studied. Android and gynoid fat distribution were determined by dual X-ray absorptiometry and plasma GRP78 levels were measured. Results: GRP78 plasma levels were significantly higher in patients with endometrial cancer as compared to the control group. Android fat distribution had a positive correlation with plasma GRP78 levels (p<0.01). Gynoid fat had a negative correlation with plasma GRP78 levels (p<0.01). Conclusions: GRP78 levels are associated with the distribution of adipose tissue and are higher in patients with endometrial cancer.

Antecedentes: La asociación de obesidad con cáncer endometrial puede depender de la presencia de estrés del retículo endoplásmico (RE) en el adipocito. La proteína 78 regulada por glucosa (GRP78) es un marcador de estrés del RE. Esta proteína regula el estrés de RE gracias a su rol antiaopoptótico. Ella juega un rol en el desarrollo, progresión y quimio-resistencia de tumores. Objetivo: Buscar una asociación entre obesidad androide o ginoide, niveles plasmáticos de GRP78 y cáncer endometrial. Material y métodos: Se estudiaron 44 mujeres con cáncer endometrial de 72 ± 6 años and 44 mujeres sanas de 55 ± 9 años. La distribución androide o ginoide de la grasa fue determinada por densitometría radiológica de doble fotón (DEXA) y se midieron los niveles plasmáticos de GRP78. Resultados: Los niveles de GRP78 fueron significativamente más altos en mujeres con cáncer endometrial. Se observó una correlación positiva entre la distribución de grasa androide y los niveles de GRP78 (p< 0.01). Se observó una correlación negativa entre distribución de grasa ginoide y niveles de GRP78. Conclusiones: Los niveles de GRP78 se correlacionan con la distribución del tejido adiposo y son mayores en mujeres con cáncer endometrial.

possible renoprotective effect of some drugs inducing heat shock proteins in renal ischemic reperfusion injury in rats

Renal ischemia reperfusion [RIRI] injury is a clinically important problem. The aim of this study was to assess the possible renoprotective effect of inducing heat shock proteins by hydrocortisone and acetylsalicylic acid [ASA] in RIRI in rats. The present study was conducted on 56 male albino rats that were divided into four groups. Group I included normal Sham-operated rats that served as control for group II, Group II was subdivided into Group IIa in which renal ischemia reperfusion injury [RIRI] was induced and group IIb [in which RIRI was induced and received quercetin [HSP70 inhibitor] 24 hours and again 1 hour prior to the induction of RIRI. Groups III and IV consisted of rats with RIRI that received hydrocortisone without [Group IIIa] or with [Group IIIb] quercetin, and that received ASA without [Group IVa] or with [Group IVb] quercetin, respectively, intramuscularly 24 and 12 hours before and after the induction of RIRI. Thirty hours after induction of RIRI, serum urea concentration and creatinine clearance were assessed. Moreover; renal heat shock protein-70 [HSP70] level and renal caspase-3 activity [as an index of apoptosis] were assessed. A significant increase in serum urea concentration and in renal HSP70 level, and caspase-3 activity together with a significant decrease in creatinine clearance, has been observed in non-treated rats [group II] killed 30 hrs after RIRI compared to Sham-operated rats. Administration of hydrocortisone or ASA resulted in a significant decrease in serum urea concentration and in renal caspase-3 activity as well as a significant increase in creatinine clearance and a significant increase in renal HSP70 in rats killed 30 hrs following RIRI [group III and IV] compared to non-treated rats with RIRI. Induction of HSP70 mediated the renoprotective role of both drugs evidenced by a significant decrease in renoprotective effect of either drug in the groups that received quercetin [IIIb and IVb] compared to those that didn't receive quercetin [IIIa and IVa]. This study demonstrates a role for HSP70 in protection against RIRI. Pharmacological strategies to increase stress protein expression have potential merit to prevent ischemic injury to the kidney and other organs. The ability of hydrocortisone and ASA to induce ischemic tolerance suggests that there are advantages in their application in RIRI. First, either is a safe drug in clinical practice. Second, the induction time of ischemic tolerance is relatively rapid after administration of either. Third, there is no additional or special equipment required for the induction of tolerance. Clinical studies will be necessary to evaluate the therapeutic properties of either drug in preventing I/R injury not only in kidneys but also in other solid organs

Antibodies to chlamydia trachohomatis heat shock protein 60 [chlamydial HSP 60] and chlamysia trachomatis major outer membrane proten [MOMP] in women with tubal factor infertility

Most of the acute infections of Chlamydia trachomatis are asymptomatic and are thus left untreated. In some women repeated or persistent C. trachomatis infection leads to scarring of the fallopian tube tissue and subsequent infertility because of occlusion of the tubes. Screening for C trachomatis specific antibodies is mandatory in. diagnosing asymptomatic tubal factor infertility [TFI], particularly because it has been shown that C trachomatis is rarely isolated from the upper genital tract and clinical diagnosis requires invasive procedures not routinely available in general practice. C. trachomatis has immunodominant proteins such as major outer membrane protein [MOMP] and Chlamydial heat shock protein6o [chlamydial hsp60] that most of the host's immune response is directed at. The aim of the present study was to evaluate the association between, antibodies to C. trachomatis-specific IgG and chlamydial hsp60 in women with TFI. This study was done on 45 women diagnosed as having TFI by means of hysterosalpingogram [HSG] and laparoscopy, and 31 wives of male factor infertility patients with documented patent tubes by hysterosalpingogram, as a control group. Their age ranged from 19 to 35 years. Antibodies to C. trachomatis-specific IgG were more prevalent in younger women [<25 years old] than older women [>25 years old]. 77% versus 47% in TFI group, and 37% versus 27% in control group. Antibodies to C. trachomatis specific IgG were present in 29 [64%] of 45 women with tubal infertility compared with 10 [32%] of 31 control women. The difference was statistically significant [P=0, 0019]. antibodies to chlamydial hsp60 were significantly higher in TFI patients [28 of 45; 62%] than controls [6 of 31; 20%]. The difference was satistica1ly significant [P 0, 0002], Using the Spearman rank order correlation test, the antibodies chlamydial hsp6o had a highly significant correlation to C. trachomatis specific IgG antibodies in TFI patients [rs 0.53, P<0.001] and in controls [rs= 0.54, P<0.001]. In conclusion, Antibodies to chlamydial hsp60 and C. trachomatis-specific IgG are strongly associated with TFI a when used in combination at initial infertility evaluation, they would provide a rapid non-interventive means of diagnosing tubal factor infertility

Expression of heat shock proteins and its clinical relevance in rheumatic diseases

Rheumatic diseases [RDs] are characterized by acute and chronic inflammation, and autoimmunity plays a major role in their pathogenesis. The presence of antibodies against heat shock proteins [HSPs] has been reported to occur in several autoimmune rheumatic diseases. This study assesses the expression of HSPs [70 and 90 KD] in the peripheral blood mononuclear cells [PBMCs] of patients with rheumatoid arthritis [RA] [n=20], and systemic lupus erythematosus [SLE] [n=20], as compared to osteoarthritis [OA] [n=20] and normal control volunteers [n=20]. Expression of HSPs was analyzed using protein electropheresis and immunoblotting techniques. The results revealed that HSP 90 is expressed in 40% of lupus patients versus 20, 10 and 5% in rheumatoid, osteoarthritis and normal controls [P<0.05]. Yet, both HSP 90 and 70 expression cannot differentiate between active and non active lupus patients. The erythrocyte sedimentation rate was the only laboratory test that showed significant difference [P< 0.01] between HSP +ve and -ve lupus patients. As regards rheumatoid arthritis and osteoarthritic patients, no increase of HSP expression could be detected when compared to normal controls. It is concluded that HSP 90 expression is more likely to differentiate lupus patients from normal controls as well as patients with other rheumatic diseases. However, it cannot be used to assess the clinical state of the disease