Biological component of the NIMH clinical research branch collaborative program on the psychobiology of depression: II. Methodology and data analysis

A preceding paper has reviewed the history, background, and rationale for this collaborative effort exploring the biologic basis of the affective disorders. This paper details the "flow" of a subject through the experimental protocol, the instrumentation used to obtain the clinical and behavioural data, and the biologic methodologies employed in the analysis of the body fluids. Data management and analysis techniques developed for this study are also examined.     

Health-Related Predictors of Quality of Life in Cancer Patients in Saudi Arabia

Research on Saudi Arabian cancer patients is a priority at King Abdulaziz Medical City (KAMC), Riyadh, Saudi Arabia. Because there is limited research on the quality of life (QoL) of Saudi Arabian cancer patients, the aim of this study was to identify the predictors of the QoL in a sample of Saudis with cancer. In August 2016, a cross-sectional study was conducted on 438 patients with a variety of cancer types (145 breast, 109 colorectal, 38 leukemia, 45 lymphoma, and 99 other types) who attended the Oncology Outpatient Clinics at KAMC. Sociodemographics, clinical symptoms, and cancer treatments were collected for each patient. We used the SF-36 instrument to assess QoL. Of the cancer patients studied, 28.4% had a family history of cancer, and, according to subgroup analyses, the elderly, those lacking formal education, the unemployed, those diagnosed with Stage III/IV, and those with metastasis had significantly worse physical functions than the other cancer patients. According to multiple linear regression analyses, cancer patients who exercised regularly tended to have better physical function, emotional role function, vitality, social function, and general health (increase in SF-36 scores of 8.82, 9.75, 5.54, 6.66, and 4.97, respectively). Patients with first-year-after-cancer diagnosis tended to have poor emotional wellbeing, social function, and general health (decrease in SF-36 scores of 5.20, 7.34, and 6.12, respectively). Newly diagnosed cancer patients and patients who did not exercise tended to experience significantly poor QoL in several domains; thus, the effectiveness of exercise must be assessed in Saudi cancer patients as an intervention to improve QoL.     

Meta-Analysis and Systematic Review of Micro- and Macro-Nutrient Intakes and Trajectories of Macro-Nutrient Supply in the Eastern Mediterranean Region

The Eastern Mediterranean Region (EMR) is experiencing a nutrition transition, characterized by the emergence of overnutrition and micro-nutrient deficiencies. No previous study has comparatively examined nutrient intake in adults across countries in the EMR. This review examined the adequacy of nutrients in adults living in the EMR. Moreover, it analyzed the food balance sheets (FBS) for 1961–2018 to identify the trajectory of energy supply from macro-nutrients in the EMR. A systematic search was conducted from January 2012 to September 2020. Only observational studies were retained with a random sampling design. An assessment of the methodological quality was conducted. Levels of nutrient daily intake and their adequacy compared to the daily reference intake of the Institute of Medicine were reported across the region. No studies were identified for half of the region’s countries. Although nutrient energy intake was satisfactory overall, fat and carbohydrate intake were high. Intake of vitamin D, calcium, potassium, zinc, and magnesium were below that recommended. The analysis of the FBS data allowed for the identification of four linear patterns of trajectories, with countries in the EMR best fitting the ‘high-energy-supply from carbohydrate’ group. This systematic review warrants multi-sectorial commitment to optimize nutrient intake.     

Formation and degradation of 1-(ethyl)-1-(2-hydroxyethyl) aziridinium chloride in aqueous media--a comparative NMR study

The formation and decomposition of 1-(ethyl)-1-(2-hydroxyethyl) aziridinium chloride in aqueous media (10 mM solutions) was studied by NMR spectroscopy. Compared to 1-diethyl aziridinium chloride which lacks the hydroxyl group, the degradation of the title compound at 37 degrees C and pH = 7.4 is about 10 times faster. However, liquid nitrogen frozen solutions of both aziridinium salts are stable for long periods of time (1-6 months).     

Central neurotransmitter effects of organotin compounds: trials, tribulations and observations

Administration of trimethyltin (TMT) or triethyltin (TET) compounds to rats during postnatal development has known behavioral and neuropathological consequences. By measuring the concentrations of dopamine, norepinephrine, homovanillic acid, dihydroxyphenylacetic acid, gamma-aminobutyric acid, acetylcholine, and choline in different brain areas of TMT and TET-treated animals, an attempt was made to correlate these functional deficits with changes in CNS neurotransmitter alterations in vivo. TET had no effect on any of the substances measured whereas TMT significantly decreased gamma-aminobutyric acid and dopamine levels, but only in hippocampus and striatum, respectively. All other neurotransmitter substances measured were not affected. These findings illustrate the complexity inherent in attempting to use neurochemical techniques alone as an index of toxicity in the absence of specific defined hypotheses.     

Development of a sensitive and inexpensive micropush-pull technique for the continuous analysis of brain neurotransmitters and metabolites in vivo.

A new, sensitive, convenient, inexpensive and low-maintenance miniaturized triple-cannula system (Zhange et al., 1990) for the push-pull perfusion of brain tissue has been constructed, and tested for its ability to exchange substances in rats, both in vitro and in vivo. In vitro: the cannula was immersed in a vial filled with 1.5 ml of a 1 microM standard solution of norepinephrine, dopamine, and their metabolites. Artificial cerebrospinal fluid was perfused through the system. Perfusate was collected at rates of 1, 2, 5, 10 and 20 microliters/min over 10 min. The recovery rate of the biogenic amines (using high performance liquid chromatography) at 10-min intervals for 60 min was consistent (57 +/- 1.31%) in low flow rate groups (1 approximately 10 microliters/ml). In vivo: [3H]choline (3 microCi, 35 nmol) was infused (6 min) into the lateral ventricle and collected by micropush-pull at 10-min intervals for 180 min, from the cerebellomedullary cistern and hippocampus. The highest [3H]choline count was reached within 10 min after infusion. Levels returned to baseline within 20 min following infusion of the tracer. The micropush-pull cannula was also adapted for chronic brain perfusion in vivo. Recovery of perfused fast green dye (0.00025%) was comparable (83 +/- 1.75%), using the same cannula for 3 sampling periods within 1 month in a freely moving rat. A cresyl violet analysis showed minimal damage to the brain tissue, with gliosis only evident in a narrow margin along the cannula track. Thus the micropush-pull technique is highly efficient in terms of exchange of material, causes minimal damage of brain tissue, and can be used chronically in awake animals. These data have been presented in preliminary form at the 1991 ASPET meetings (Zhang et al., 1991).     

Effects of immobilization stress on hippocampal monoamine release: Modification by mivazerol, a new α2-adrenoceptor agonist

Mivazerol is a new and selective α₂-adrenoceptor agonist which has demonstrated anti-ischemic effects, both in animals and in patients with myocardial ischemia. In the present study, mivazerol was evaluated for its ability to inhibit the release of catecholamines and serotonin (5-HT) in the hippocampus of freely moving rats, and also was compared to clonidine. In vivo microdialysis in combination with high-performance liquid chromatography (HPLC) was employed. Intravenous administration of mivazerol (8.0 μg/kg) had no effect on basal outflow of norepinephrine (NE), dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC). In contrast, clonidine (8.5 μg/kg, i.v.) attenuated the basal release of DOPAC, which has been proposed to reflect NE biosynthesis, suggesting that clonidine has an inhibitory effect on NE synthesis. In addition, both mivazerol and clonidine decreased the spontaneous release of 5-HT, which provided further evidence that α₂-adrenoceptors in the hippocampus modulate 5-HT. Sixty-min immobilization stress significantly increased the release of NE (177 ± 28%), DA (209 ± 46%) and DOPAC (337 ± 72%). Mivazerol (2.5, 8.0 and 25 μg/kg, i.v.) completely prevented the immobilization stress-induced enhancement of NE, DA and DOPAC, which was equi-effective to clonidine at a dose of 8.5 gmg/kg, i.v. These findings demonstrate that mivazerol has a profound modulatory effect on stress-induced neurotransmitter release in the hippocampus, at dose levels reported to protect against myocardial ischemia.