Adiponectin and leptin profiles among obese pregnant women with preeclampsia vs. non-preeclampsia: a systematic review and meta-analysis.

OBJECTIVE: Preeclampsia (PE) affects only about 10% of women who meet the criteria for obesity based on their body mass index (BMI). Obesity is suggested to play a role in preeclampsia pathophysiology, and in addition to BMI, associated biomarkers with higher sensitivity and specificity, such as with adipokines from adipose tissue, are needed to enable clinical risk assessment. This study aimed to investigate obese pregnant women with and without PE by comparing clinical profiles and adipokine profiles specific to general adipose tissue (adiponectin and leptin). MATERIALS AND METHODS: This meta-analysis was conducted following the PRISMA and was registered in PROSPERO (CRD42023478706). We utilized Cochrane, Scopus, and PubMed/Medline databases. The Cochrane ROBINS-I instrument was employed to assess the quality of studies. Pooled standard mean difference (SMD) and p-value were analyzed using a random-effects model with the DerSimonian-Laird method, while subgroup analysis with the Chi-square test and the inconsistency index (I2) were used to assess potential sources of heterogeneity. RESULTS: Three observational studies included a total of 2,646 obese pregnant women and found that adiponectin was more likely to have a lower level in pregnant women with obesity [SMD=-0.32; 95% CI: -0.34-0.17, p=0.003] and leptin was more likely to be higher in obese pregnant women with PE rather than non-PE [SMD=0.53; 95% CI: -0.19-1.08, p<0.00001]. CONCLUSIONS: Adiponectin levels were more likely to be lower in pregnant women with obesity in the PE group than in the non-PE group, and leptin levels were more likely to be higher.

Crocetin exerts hypocholesterolemic effect by inducing LDLR and inhibiting PCSK9 and Sortilin in HepG2 cells.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an important post-transcriptional regulator of plasma levels of low-density lipoprotein cholesterol (LDL-C). Inhibition of PCSK9 has emerged as an attractive strategy in recent years to combat hypercholesterolemia stimulating the search for PCSK9 inhibitors. The carotenoid crocetin exhibits hypocholesterolemic effect. However, it is unknown whether the beneficial effect is mediated through PCSK9 modulation. We hypothesized that crocetin inhibits PCSK9 and therefore, in our quest for natural and safe PCSK9 inhibitors, we investigated crocetin on PCSK9 expression and other key molecular targets involved in hepatic cholesterol metabolism using the human hepatoma cell line HepG2 as a model system. We demonstrate for the first time that crocetin treatment significantly decreases PCSK9 and sterol regulatory element binding proteins (SREBP) expression in a dose-dependent manner, accompanied by a concomitant increase in the hepatic low-density lipoprotein receptor (LDLR) expression. Additionally, crocetin significantly downregulates the levels of both mRNA and protein expression of sortilin, a key sorting receptor that facilitates PCSK9 transport in the trans Golgi network in a dose dependent manner. Overall, our results suggest that crocetin is a LDLR inducer, and an inhibitor of PCSK9, sortilin and SREBPs, thus making it an effective natural anti-cholesterol agent.

Compression moulding and injection over moulding of porous PEEK components.

A simple and adaptable process for the production of porous PEEK has been demonstrated herein, which uses compression moulding to infiltrate molten PEEK into of a packed bed of salt beads. The process has the capacity to vary the pore size and porosity within the range suitable for materials to replace bone, but compressive testing showed the stiffness to be well below the target to match trabecular bone. This issue was addressed by creating a hybrid structure, integrating "pillars" of solid PEEK into the porous structure, by the injection over-moulding of compression moulded PEEK-salt inserts that contained drilled holes. Good bonding between the moulding and the insert was demonstrated and it was found that as little as 35 mm2 of support, in the form of PEEK "pillars" was required to achieve the target performance.

The mobile-phone-based iCOTM Smokerlyzer®: Comparison with the piCO+ Smokerlyzer® among smokers undergoing methadone-maintained therapy.

INTRODUCTION: The mobile-phone-based Bedfont iCOTM Smokerlyzer® is of unknown validity and reproducibility compared to the widely-used piCO+ Smokerlyzer®. We aimed to compare the validity and reproducibility of the iCOTM Smokerlyzer® with the piCO+ Smokerlyzer® among patients reducing or quitting tobacco smoking. METHODS: Methadone-maintained therapy (MMT) users from three centers in Malaysia had their exhaled carbon monoxide (eCO) levels recorded via the piCO+ and iCOTM Smokerlyzers®, their nicotine dependence assessed with the Malay version of the Fagerström Test for Nicotine Dependence (FTND-M), and daily tobacco intake measured via the Opiate Treatment Index (OTI) Tobacco Q-score. Pearson partial correlations were used to compare the eCO results of both devices, as well as the corresponding FTND-M scores. RESULTS: Among the 146 participants (mean age 47.9 years, 92.5% male, and 73.3% Malay ethnic group) most (55.5%) were moderate smokers (6-19 cigarettes/day). Mean eCO categories were significantly correlated between both devices (r=0.861, p<0.001), and the first and second readings were significantly correlated for each device (r=0.94 for the piCO+ Smokerlyzer®, p<0.001; r=0.91 for the iCOTM Smokerlyzer®, p<0.001). Exhaled CO correlated positively with FTND-M scores for both devices. The post hoc analysis revealed a significantly lower iCOTM Smokerlyzer® reading of 0.82 (95% CI: 0.69-0.94, p<0.001) compared to that of the piCO+ Smokerlyzer®, and a significant intercept of -0.34 (95% CI: -0.61 - -0.07, p=0.016) on linear regression analysis, suggesting that there may be a calibration error in one or more of the iCOTM Smokerlyzer® devices. CONCLUSIONS: The iCOTM Smokerlyzer® readings are highly reproducible compared to those of the piCO+ Smokerlyzer®, but calibration guidelines are required for the mobile-phone-based device. Further research is required to assess interchangeability.

Influence of pH on interaction of silver nanoparticles - protein: Analyses by spectroscopic and thermodynamic ideology.

To investigate the interaction between bovine serum albumin (BSA) and silver nanoparticles (AgNPs) at five different pHs (below (3.0 and 4.0), above (7.4 and 9.2) and at the isoelectric point (4.7) of BSA) by spectroscopic (viz., UV-vis, fluorescence, circular dichroism (CD)), microscopic (viz., atomic force microscopy (AFM), transmission electron microscopy (TEM), field emission scanning electron microscope (FESEM)) and thermodynamic (viz., isothermal titration calorimetry (ITC)) methods. The fluorescence quenching spectra provided binding constants via Stern-Volmer plot, quenching constant (Ksv) and rate constant (Kq) were calculated. From the CD spectra, it is clear that the α-helix decreases by increasing the AgNP's concentration. However, at isoelectric point (pH = 4.7), BSA shows more helicity in the presence of AgNPs, which indicates that the structures of BSA become more ordered and stable, and aggregation occurs at strong acidic (3.0), and basic medium (9.2) Fluorescence spectra also indicate the aggregation of the protein at strong acidic (pH = 3.0) and basic medium (pH = 9.2). Furthermore, the morphological and topographical evolute ion upon the interaction was examined using TEM, FESEM, and AFM. The studies conclude the effect of the pH in the medium and behavior of AgNPs with BSA by using different spectroscopic and microscopic techniques.

Immuno-modulating properties of Tulathromycin in porcine monocyte-derived macrophages infected with porcine reproductive and respiratory syndrome virus.

Porcine reproductive and respiratory syndrome virus (PRRSV) is a positive-stranded RNA virus that grows in macrophages and causes acute pneumonia in pigs. PRRSV causes devastating losses to the porcine industry. However, due to its high antigenic variability and poorly understood immunopathogenesis, there is currently no effective vaccine or treatment to control PRRSV infection. The common occurrence of PRRSV infection with bacterial infections as well as its inflammatory-driven pathobiology raises the question of the value of antibiotics with immunomodulating properties for the treatment of the disease it causes. The macrolide antibiotic Tulathromycin (TUL) has been found to exhibit potent anti-inflammatory and immunomodulating properties in cattle and pigs. The aim of this study was to characterize the anti-viral and immunomodulating properties of TUL in PRRSV-infected porcine macrophages. Our findings indicate that blood monocyte-derived macrophages are readily infected by PRRSV and can be used as an effective cellular model to study PRRSV pathogenesis. TUL did not change intracellular or extracellular viral titers, not did it alter viral receptors (CD163 and CD169) expression on porcine macrophages. In contrast, TUL exhibited potent immunomodulating properties, which therefore occurred in the absence of any direct antiviral effects against PRRSV. TUL had an additive effect with PRRSV on the induction of macrophage apoptosis, and inhibited virus-induced necrosis. TUL significantly attenuated PRRSV-induced macrophage pro-inflammatory signaling (CXCL-8 and mitochondrial ROS production) and prevented PRRSV inhibition of non-opsonized and opsonized phagocytic function. Together, these data demonstrate that TUL inhibits PRRSV-induced inflammatory responses in porcine macrophages and protects against the phagocytic impairment caused by the virus. Research in live pigs is warranted to assess the potential clinical benefits of this antibiotic in the context of virally induced inflammation and tissue injury.

Counterion coupled (COCO) gemini surfactant capped Ag/Au alloy and Ag@Au core-shell nanoparticles for cancer therapy.

Hybrid silver (Ag)-gold (Au) nanoparticles (NPs) with different sizes and compositions were synthesized. Ag/Au alloy and Ag@Au core-shell type NPs were prepared from Ag and Au with various ratios using the COCO gemini surfactant, 1,6-bis (N,N-hexadecyldimethylammonium) adipate (COCOGS), 16-6-16 as a stabilizer. The formation of the Ag/Au alloy and Ag@Au core-shell was confirmed by UV-visible absorption spectroscopy, high-resolution transmission electron microscopy (HRTEM), energy-dispersive X-ray spectroscopy (EDX) and selected area electron diffraction (SAED) patterns. Depending on the composition of the Ag/Au alloy NPs, the λ max values varied from 408 nm to 525 nm. FTIR measurements were used to evaluate the adsorption of the COCO gemini surfactant (16-6-16) on the Ag/Au alloy and Ag@Au core-shell surface. In this present work, we study how to achieve the stability and activity of the COCO gemini surfactant (16-6-16) capped Ag/Au alloy and Ag@Au core-shell NPs for developing novel anti-cancer agents by evaluating their potentials in the Hep-2 cell line model. Thus the developed core-shell NPs were possibly involved in inducing cytotoxicity followed by inhibition of cell proliferation to the cancer cells with apoptosis induction. The developed core-shell NPs might serve as highly applicable agents in the development of next-generation cancer chemotherapeutic agents.

Effect of gemini surfactant (16-6-16) on the synthesis of silver nanoparticles: A facile approach for antibacterial application.

In this report, we describe the effect of Gemini surfactants1, 6-Bis (N, N-hexadecyldimethylammonium) adipate (16-6-16) on synthesis, stability and antibacterial activity of silver nanoparticles (AgNPs). The stabilizing effect of Gemini surfactant and aggregation behavior of AgNPs was evaluated by plasmonic property and morphology of the AgNPs were characterized by UV-vis spectroscopy, Dynamic Light Scattering (DLS), X-ray diffraction (XRD), High resolution transmission electron microscopy (HRTEM) and Energy dispersive X-ray analysis (EDX) techniques. Interestingly, the formation of quite mono-dispersed spherical particles was found. Apart from the stabilizing role, the Gemini surfactant has promoted the agglomeration of individual AgNPs in small assemblies whose Plasmon band features differed from those of the individual nanoparticles. The antibacterial activity of the synthesized AgNPs on Gram-negative and Gram-positive bacterium viz., E. coli and S. aureus was carried out by plate count, growth kinetics and cell viability assay. Furthermore, the mechanism of antibacterial activity of AgNPs was tested by Zeta potential and DLS analysis, to conclude that surface charge of AgNPs disrupts the cells causing cell death.

Medicinal chemistry of antimigraine drugs.

Migraine is one of the most frequent neurological disorder with high impact on the quality of life. Primary headaches such as migraine are pathophysiologically complex disorders. The concept of the trigeminovascular system dysfunction in migraine has led to a number of drug discoveries dramatically changing the treatment options. Acute and prophylactic therapy targeting either the trigeminovascular system or central structures involve several groups of drugs with peculiar medicinal chemistry. In the proposed review up to date concept of treatment strategy, medicinal chemistry data of the drugs used will be summarized. The present review gives detailed information on drugs effective in aborting migraine attacks (by inhibiting prostanoid synthesis, are agonists of serotonin 5-HT1B/D receptors, on the recently introduced CGRP-receptor antagonists) and the drugs recommended for prophylactic treatment (selected beta-adrenergic receptor antagonists, Ca-channel inhibitors, antiepileptics, antidepressants). The pharmacokinetics, fate in the body (absorption, distribution, metabolism, excretion) and significant pharmacological effects as well as the recent bioanalytical methods for their determination are presented.

Study on medicinal chemistry of K203 in wistar rats and beagle dogs.

K203 is an experimental bis-pyridinium mono-aldoxime type cholinesterase reactivator of potential use in organophosphate/ organophosphonate poisoning. Pharmacokinetics of K203 were examined in Wistar rats and beagle dogs using ion-pair HPLC. Serum and cerebrospinal fluid concentrations of K203 were determined using ion-pair reversedphase chromatography on octadecyl silica column. HPLC with ultraviolet detection was used for determination of serum concentration of K203 higher than 0.1 µg/mL while its low concentrations in cerebrospinal fluid required electrochemical detection (0.015 through 4 µg/mL range). In rats the serum levels of K203 followed zero order pharmacokinetics from 15 to 120 minutes post administration. Zero order pharmacokinetics was also observed in beagle dogs after low dose (15 µmol/kg) of K203 administration. High dose administration (250 µmol/kg) led to subsequent hindered elimination from both cerebrospinal fluid and serum.

Juvenile onset ankylosing spondylitis with ankylosing tarsitis: a rare combination.

Ankylosing spondylitis is the most common whereas ankylosing tarsitis is the least common subgroup of juvenile onset spondyloarthritides. In our recent study a male presented with ankle joint pain and swelling with limited movements and characteristic radiological changes including; periarticular swelling, thickened heel pad, hyperostosis and reduced ankle, calcaneo-cuboid and talo-navicular joint space for ankylosing tarsitis. He also had persistent inflammatory low back pain with radiological sacroilitis satisfying the clinical features for ankylosing spondylitis. The patient was treated with different anti-inflammatory agents including intra-articular methyl-prednisolone with short-term relief. Associated back pain was improved with spine mobilizing exercise.

Candidate DNA methylation drivers of acquired cisplatin resistance in ovarian cancer identified by methylome and expression profiling.

Multiple DNA methylation changes in the cancer methylome are associated with the acquisition of drug resistance; however it remains uncertain how many represent critical DNA methylation drivers of chemoresistance. Using isogenic, cisplatin-sensitive/resistant ovarian cancer cell lines and inducing resensitizaton with demethylating agents, we aimed to identify consistent methylation and expression changes associated with chemoresistance. Using genome-wide DNA methylation profiling across 27 578 CpG sites, we identified loci at 4092 genes becoming hypermethylated in chemoresistant A2780/cp70 compared with the parental-sensitive A2780 cell line. Hypermethylation at gene promoter regions is often associated with transcriptional silencing; however, expression of only 245 of these hypermethylated genes becomes downregulated in A2780/cp70 as measured by microarray expression profiling. Treatment of A2780/cp70 with the demethylating agent 2-deoxy-5'-azacytidine induces resensitization to cisplatin and re-expression of 41 of the downregulated genes. A total of 13/41 genes were consistently hypermethylated in further independent cisplatin-resistant A2780 cell derivatives. CpG sites at 9 of the 13 genes (ARHGDIB, ARMCX2, COL1A, FLNA, FLNC, MEST, MLH1, NTS and PSMB9) acquired methylation in ovarian tumours at relapse following chemotherapy or chemoresistant cell lines derived at the time of patient relapse. Furthermore, 5/13 genes (ARMCX2, COL1A1, MDK, MEST and MLH1) acquired methylation in drug-resistant ovarian cancer-sustaining (side population) cells. MLH1 has a direct role in conferring cisplatin sensitivity when reintroduced into cells in vitro. This combined genomics approach has identified further potential key drivers of chemoresistance whose expression is silenced by DNA methylation that should be further evaluated as clinical biomarkers of drug resistance.

International surgery: causes of hand injuries in a developing country.

BACKGROUND: In emerging economies such as Nigeria, trauma and hand injuries in particular are on the rise. The aim of this study was to document the causes of hand injuries in Nigeria. METHODS: This was a prospective study conducted between Aug. 1, 2006, and July 31, 2007. We obtained objective information about patient demographic data, occupation, dominant and injured hand, and place and cause of injury. We assessed injury severity using the Hand Injury Severity Score (HISS). RESULTS: A total of 74 patients with hand injuries were included. The male:female ratio was 1.8:1, and the average age was 26.9 years. Most patients were right-hand dominant, and 56.8% of injuries affected the dominant hand. Engineers and technicians represented 27% of patients with hand injuries, which was the largest group encountered during the study. Most cases occurred because of road traffic injuries, followed by machine injuries. Injuries commonly occurred at the work place and on the road. In total, 57.1% of patients with mechanical injuries were admitted to hospital. The majority received minor surgical treatment, and 16.2% had a digit amputated. The average HISS was 54.35. In total, 64.8% of the injuries were classified as minor or moderate. Sixty percent of admissions were patients with a HISS of severe or major injury. CONCLUSION: Hand injury in this part of the world is commonly due to road traffic collisions and machine accidents, and the injuries are usually severe. Hand injuries are commonly seen among technicians and civil or public servants; these people constitute the economic work force.

Osteopoikilosis.

Osteopoikilosis is very rare autosomal dominant disorder of unknown etiology which is found incidentally on radiological examination. It is also known as Albers-Schonberg disease or osteopathia condensans disseminata, characterized by the presence of multiple and often symmetrical radio-dense lesion in osseous tissue. Here we report a case of osteopoikilosis in a 30 years old man presented with left hip joint pain and restricted movements. Radiological study showed typical features of osteopoikilosis. Necessary investigations were done to exclude osteoblastic metastasis, tuberous sclerosis and synovial chondromatosis. The patient was treated with pharmacological and non-pharmacological approach with significant improvement of joint pain and movements.

Validation of the Malay version of the Multidimensional Scale of Perceived Social Support (MSPSS-M) among a group of medical students in Faculty of Medicine, University Malaya.

OBJECTIVE: The aim of this study was to validate the Malay version of the Multidimensional Scale of Perceived Social Support (MSPSS-M) among a group of medical students in Faculty of Medicine, University Malaya. METHODS: 237 students participated in the study. They were given the Malay version of MSPSS, medical outcome study (MOS) social support survey, Malay version of General Health Questionnaire (GHQ), Malay version of Beck Depression Inventory (BDI) and English version of MSPSS. A week later, these students were again given the Malay version of MSPSS. RESULTS: The instrument displayed good internal consistency (Cronbach's alpha=0.89), parallel form reliability (0.94) and test-retest reliability (0.77) (Spearman's rho, p<0.01). The negative correlation of the total and subscales of the instrument with the Malay version of GHQ and BDI confirmed its validity. Extraction method of the 12 items MSPSS using principle axis factoring with direct oblimin rotation converged into three factors of perceived social support (Family, Friends and Significant Others) with reliability coefficients of 0.88, 0.82 and 0.94, respectively. CONCLUSION: The Malay version of the MSPSS demonstrated good psychometric properties in measuring social support among a group of medical students from Faculty of Medicine, University Malaya and it could be used as a simple instrument on young educated Malaysian adolescents.

Acetylenic anticancer agents.

This review is a comprehensive survey of acetylenic anticancer agents obtained from living organisms. Acetylenic metabolites belong to a class of molecules containing triple bond(s). They are found in plants, fungi, microorganisms, and marine invertebrates. Although acetylenes are common as components of terrestrial plants, fungi, and bacteria, it is only within the last 30 years that biologically active polyacetylenes having unusual structural features have been reported from plants, cyanobacteria, algae, invertebrates, and other sources. Naturally occurring aquatic acetylenes are of particular interest since many of them display important biological activities and possess antitumor, antibacterial, antimicrobial, antifungal, phototoxic, HIV inhibitory, and immunosuppressive properties. There is no doubt that they are of great interest, especially for the medicinal chemistry, and/or pharmaceutical industries. This review presents structures and describes cytotoxic activities of more than 300 acetylenic metabolites isolated from living organisms.

Single nucleotide polymorphisms in the neuropeptide Y2 receptor (NPY2R) gene and association with severe obesity in French white subjects.

AIMS/HYPOTHESIS: Genetic variants of genes for peptide YY (PYY), neuropeptide Y2 receptor (NPY2R) and pancreatic polypeptide (PPY) were investigated for association with severe obesity. SUBJECTS AND METHODS: The initial screening of the genes for variants was performed by sequencing in a group of severely obese subjects (n=161). Case-control analysis of the common variants was then carried out in 557 severely obese adults, 515 severely obese children and 1,163 non-obese/non-diabetic control subjects. Rare variants were genotyped in 700 obese children and the non-obese/non-diabetic control subjects (n=1,163). RESULTS: Significant association was found for a 5' variant (rs6857715) in the NPY2R gene with both severe adult obesity (p=0.002) and childhood obesity (p=0.02). This significant association was further supported by a pooled allelic analysis of all obese cases (adults and children, n=928) vs the control subjects (n=938) (p=0.0004, odds ratio=1.3, 95% CI 1.1-1.5). Quantitative trait analysis of BMI and WHR was performed and significant association was observed for SNP rs1047214 in NPY2R with an increase in WHR in the severely obese children (co-dominant model p=0.005, recessive model p=0.001). Association was also observed for an intron 3 variant (rs162430) in the PYY gene with childhood obesity (p=0.04). No significant associations were observed for PPY variants. Only one rare variant in the NPY2R gene (C-5641T) was not found in lean individuals and this was found to co-segregate with obesity in one family. CONCLUSIONS/INTERPRETATION: These results provide evidence of association for NPY2R and PYY gene variants with obesity and none for PPY variants. A rare variant of the NPY2R gene showed evidence of co-segregation with obesity and its contribution to obesity should be investigated further.

A 2-year follow-up of orphans' competence, socioemotional problems and post-traumatic stress symptoms in traditional foster care and orphanages in Iraqi Kurdistan.

BACKGROUND: This paper aims to compare orphans' development in two different care systems. METHODS: Based on age, sex, psychological trauma scores, competence and psychological problem scores, two comparable samples were found representing orphans in the traditional foster care (n = 94) and the orphanages (n = 48) in a middle-large city in Iraqi Kurdistan. At an index interview, Child Behaviour Checklist (CBCL), Harvard-Uppsala Trauma Questionnaire for Children and Post-traumatic Stress Symptoms for Children (PTSS-C) were administered to the caregivers. After 1 year the CBCL, and after 2 years both the CBCL and the PTSS-C, were-re-administered, consecutively. RESULTS: Although both samples revealed significant decrease in the means of total competence and problem scores over time, the improvement in activity scale, externalizing problem scores and post-traumatic stress disorder-related symptoms proved to be more significant in the foster care than in the orphanages. While the activity scale improved in the foster care, the school competence deteriorated in both samples, particularly among the girls in the orphanages. The improvement of boys' activity scores in the foster care, and deterioration of girls' school competence in the orphanages were the most significant gender differences between samples over time. CONCLUSIONS: Even if the two orphan care systems showed more similarities than differences, the foster care revealed better outcomes over time. The results are discussed in relation to gender, age, socio-economic situation, cultural values and the characteristics of each care system.

Unusual radiological presentation of renal cell carcinoma.

We present an unusual case of renal cell carcinoma in a 59-year-old Saudi male less than 3 cm in size showing a pelvicalyceal filling defect on excretory urography and retrograde pyelography. Renal stones and blood clots were excluded by ultrasound and computerized tomography scanning. A urothelial tumor was initially diagnosed; finally surgery revealed a papillary renal cell carcinoma.

The human homolog of Diminuto/Dwarf1 gene (hDiminuto): a novel ACTH-responsive gene overexpressed in benign cortisol-producing adrenocortical adenomas.

To elucidate the molecular mechanism of the pathogenesis of benign functioning adrenocortical adenomas causing Cushing's syndrome, we employed suppression PCR-based cDNA subtractive hybridization to identify novel genes that are differentially expressed in the adenoma. In this report we describe the adenoma-specific overexpression of the human homolog of the Diminuto/Dwarf1 (hDiminuto) gene. Northern blot analysis revealed that hDiminuto mRNA was overexpressed in the adenoma tissue of 14 patients with Cushing's syndrome in comparison to the adjacent nontumorous adrenal gland. In situ hybridization using hDiminuto cRNA probe showed its abundant expression in the tumor cells, whereas the nontumorous cells showed a low level of expression. As the atrophic adjacent gland may not represent the normal architecture, we examined the expression pattern of hDiminuto mRNA in normal human adrenal cortex. In situ hybridization revealed that it was expressed in all layers of the normal adrenal cortex. In situ apoptosis detection by the TUNEL method revealed that a low level of hDiminuto expression in the atrophic, adjacent gland was associated with numerous TUNEL-positive cells in all layers of cortex. In contrast almost no apoptotic cell was detected in the tumor or in the normal adrenal cortex where hDiminuto expression was abundant. These results are compatible with a recent report that hDiminuto acts as an antiapoptotic factor in neurons. The expression of hDiminuto in the normal adrenal cortex was most abundant in the zona fasciculata, suggesting its possible regulation by ACTH/cAMP. Indeed, forskolin treatment of H295R human adrenocortical cells resulted in a significant induction of the mRNA in a time- and dose-dependent manner. To further demonstrate the physiological regulation, an in vivo experiment was carried out in dexamethasone-treated rats. ACTH administration to these rats increased the mRNA expression. These results led us to speculate that the overexpression of hDiminuto in the adenoma could be due to the abundant expression of ACTH receptor, as we previously described. Diminuto is involved in steroid synthesis and cell elongation in plants. We, therefore, hypothesize that hDiminuto might be involved in the molecular events of adrenocortical tumorigenesis by facilitating steroid synthesis and cell growth.