Preparation and bioevaluation of 99mTc-carbonyl complex of 5-hydroxy tryptamine derivative.

Studies on the development of imaging agents for targeting neuroreceptors is an area of considerable interest owing to the limited availability of specific as well as selective radiolabeled agents. Therefore, with an aim of developing a receptor-specific agent, iminodiacetic acid (IDA) derivative of 5-hydroxy tryptamine viz., HTIDA has been synthesized. HTIDA could be radiolabeled with the synthon [(99m)Tc(CO)(3)(H(2)O)(3)](+) in >98% yield. The biodistribution studies in normal Swiss mice showed that the (99m)Tc(CO)(3)-HTIDA crosses the blood-brain barrier successfully with a brain uptake of 0.5%ID/g at 5min post injection. The other relevant observations from biodistribution studies included no significant uptake in any other organ and fast clearance from blood, lungs and liver.     

A tracer kinetic model for 18F-FHBG for quantitating herpes simplex virus type 1 thymidine kinase reporter gene expression in living animals using PET.

Reporter probe 9-(4-18F-fluoro-3-[hydroxymethyl]butyl)guanine (18F-FHBG) and reporter gene mutant herpes simplex virus type 1 thymidine kinase (HSV1-sr39tk) have been used for imaging reporter gene expression with PET. Current methods for quantitating the images using the percentage injected dose per gram of tissue do not distinguish between the effects of probe transport and subsequent phosphorylation. We therefore investigated tracer kinetic models for 18F-FHBG dynamic microPET data and noninvasive methods for determining blood time-activity curves in an adenoviral gene delivery model in mice. METHODS: 18F-FHBG (approximately 7.4 MBq [approximately 200 microCi]) was injected into 4 mice; 18F-FHBG concentrations in plasma and whole blood were measured from mouse heart left ventricle (LV) direct sampling. Replication-incompetent adenovirus (0-2 x 10(9) plaque-forming units) with the E1 region deleted (n = 8) or replaced by HSV1-sr39tk (n = 18) was tail-vein injected into mice. Mice were dynamically scanned using microPET (approximately 7.4 MBq [approximately 200 microCi] 18F-FHBG) over 1 h; regions of interest were drawn on images of the heart and liver. Serial whole blood 18F-FHBG concentrations were measured in 6 of the mice by LV sampling, and 1 least-squares ratio of the heart image to the LV time-activity curve was calculated for all 6 mice. For 2 control mice and 9 mice expressing HSV1-sr39tk, heart image (input function) and liver image time-activity curves (tissue curves) were fit to 2- and 3-compartment models using Levenberg-Marquardt nonlinear regression. The models were compared using an F statistic. HSV1-sr39TK enzyme activity was determined from liver samples and compared with model parameter estimates. For another 3 control mice and 6 HSV1-sr39TK-positive mice, the model-predicted relative percentage of metabolites was compared with high-performance liquid chromatography analysis. RESULTS: The ratio of 18F-FHBG in plasma to whole blood was 0.84 +/- 0.05 (mean +/- SE) by 30 s after injection. The least-squares ratio of the heart image time-activity curve to the LV time-activity curve was 0.83 +/- 0.02, consistent with the recovery coefficient for the partial-volume effect (0.81) based on independent measures of heart geometry. A 3-compartment model best described 18F-FHBG kinetics in mice expressing HSV1-sr39tk in the liver; a 2-compartment model best described the kinetics in control mice. The 3-compartment model parameter, k3, correlated well with the HSV1-sr39TK enzyme activity (r2 = 0.88). CONCLUSION: 18F-FHBG equilibrates rapidly between plasma and whole blood in mice. Heart image time-activity curves corrected for partial-volume effects well approximate LV time-activity curves and can be used as input functions for 2- and 3-compartment models. The model parameter k3 from the 3-compartment model can be used as a noninvasive estimate for HSV1-sr39TK reporter protein activity and can predict the relative percentage of metabolites.     

Preeclampsia and Chlamydia pneumoniae: is there a link?

Several parallels exist between preeclampsia and atherosclerosis. Both are multifactorial diseases that share risk factors such as obesity, insulin resistance, lipid abnormalities, and elevated serum homocysteine. There are also similarities in the biochemical changes seen in both diseases, including elevated serum triglycerides, decreased HDL cholesterol and enhanced formation of small, dense LDL particles as well as vascular atherosclerotic lesions. Chronic infection with Chlamydia pneumoniae has been linked to coronary artery disease. This study evaluated a possible link between the incidence of preeclampsia and infection with C. pneumoniae by examining the rate of seropositivity in 81 women with preeclampsia, and 206 women with normal pregnancies. Although our data confirmed well-known risk factors for preeclampsia such as obesity, diabetes, and hypertension, we found no difference in the rate of seropositivity between preeclampsia and normal pregnancy. On the contrary, the presence of chlamydial antibodies was lower in preeclampsia. Multiparous women with preeclampsia showed a significantly lower rate of seropositivity than multiparous normal women and nulliparous preeclamptics. In addition, women with a history of preeclampsia who developed preeclampsia in the current pregnancy also had a significantly lower rate of seropositivity.     

Immunomodulatory Effects of γ-HCH (Lindane) in Mice

Mice were fed for 24 weeks with three different subtoxic dosages of γ-HCH (0.012, 0.12 and 1.2 mg/kg) mixed in powdered feed. The immunological profile was assessed at an interval of one month during the entire exposure period. Both the cell mediated and humoral components of immunity showed a biphasic response characterized initially by stimulation followed by suppression in a dose dependent manner. However, γ-HCH did not affect the functional properties of peritoneal macrophages. Histological changes in lymphoid organs were in accordance with the biphasic immunomodulatory effects of γ -HCH.     

A comparison of the prevalence of rheumatoid arthritis and other rheumatic diseases amongst Pakistanis living in England and Pakistan

The impact of environmental factors on the causation of rheumatoid arthritis (RA) is thought to be considerable. We explored this by comparing the prevalence of RA amongst Pakistanis living in England, where it is relatively high amongst ethnic English, and in Pakistan. The frequency of other rheumatic diseases was also compared. Information on 2056 adult Pakistanis in England and 4232 in Pakistan was obtained by house-to-house surveys using identical protocols. Positive respondents were examined by the same two clinicians in both countries. Rheumatic complaints increased with age and were more common in females in both communities. The standardized morbidity ratio (SMR) (95% CI) of RA in England was 2.1 (1.1-3.1) compared with Pakistan, a difference that was entirely attributable to females. The SMR (95% CI) for women was 3.0 (0.4-5.6) and for men 0.86 (-0.84 to 2.56). In Pakistan, there was a trend to more reporting of some but not all rheumatic complaints amongst the affluent segment of the population. This was increasingly apparent amongst those resident in England and the possibility of an impact of easier ascertainment amongst the more educated cannot be discounted. Low back pain was significantly more common in England. Furthermore, the colder climate was frequently invoked as a cause of more symptoms in England. Thus, several factors may have influenced the observation that RA is more common amongst Pakistanis in England compared with Pakistan. An environmental factor cannot be excluded. However, the frequency of non-specific musculoskeletal pain was similar. The regions of Pakistan from which the two populations were derived were also different and immunogenetic heterogeneity might also have contributed to the difference in RA prevalence.