The effect of amphetamine sensitization on mouse immunoreactivity.

Recent studies indicate a role of the immune system in the behavioral effects of amphetamine in rodents. In the present study we attempted to find a connection between the behavioral changes induced by repeated, intermittent administration of amphetamine and some immunological consequences of sensitization to amphetamine in mice. Male Albino Swiss mice were treated repeatedly (for 5 days) with amphetamine (1 mg/kg, i.p.). On day 9, they received a challenge dose of amphetamine (1 mg/kg). Acute administration of amphetamine increased their locomotor activity by ca. 40%. In animals treated repeatedly with amphetamine, the challenge dose of the psychostimulant induced behavioral sensitization, i.e. the higher locomotor activation as compared with that after its first administration to mice. Immune functions were evaluated by the ability of splenocytes to proliferate and to produce cytokines such as interferon gamma (IFN-gamma), interleukin (IL)-4 and IL-10. Acute amphetamine administration significantly decreased, by ca. 30% and 25%, the proliferation of splenocytes in response to an optimal and a suboptimal dose of concanavalin A (Con A), respectively, and increased their ability to produce IL-4. Chronic intermittent treatment with amphetamine significantly decreased, by ca. 65% and 50%, the proliferative response of T cells to an optimal and a suboptimal dose of Con A, respectively, and diminished by 20% the metabolic activity of splenocytes. The above data showed that both acute and chronic amphetamine administration diminished some aspects of the cell-mediated immunity; nevertheless, immunosuppression was particularly evident in amphetamine-sensitized mice. Our findings seem to indicate possible importance of monitoring and correcting immune changes in the therapy of amphetamine addiction.     

Phosphorylation of guinea pig cardiac natural actomyosin and its effect on ATPase activity.

Guinea pig cardiac natural actomyosin incubated with commercial protein kinase, Mg²⁺-ATP, and cyclic AMP produced little or no change in actomyosin ATPase activity. However, addition of sodium fluoride, a known phosphatase inhibitor resulted in a decreased actomyosin ATPase at all measured calcium concentrations. The presence of phosphatase activity in actomyosin and protein kinase was confirmed with ?-nitrophenyl phosphate. These results indicate the importance of inhibiting phosphatase activity, particularly when measuring biological or enzymatic activity as a function of phosphorylation.     

氯丙嗪生态毒理效应与人体健康影响研究与展望

氯丙嗪作为一种镇静类兽药被广泛使用,其主要在肝脏中代谢,并随尿液逐渐排出;但因排出过程缓慢,容易产生药物残留。随着人们的生活质量和对动物性食品安全要求的不断提高,氯丙嗪药物残留问题受到越来越多的关注。氯丙嗪随尿液排出部分可经多种途径进入环境和人体,对生态系统和人类健康存在着潜在的威胁。本文对氯丙嗪的药物残留原因进行了分析,概述了环境中氯丙嗪的生态毒理学效应以及对人体健康的潜在影响,说明了氯丙嗪的残留与环境和人类健康有着十分密切的联系,对深入研究具有重要的现实意义。     

A health centre E.C.G. services: its use and abuse.

An average of 10-5 E.C.G.s were recorded weekly in a health centre used by 32 general practitioners serving a population of almost 65,000. The main indication for an E.C.G. was chest pain (73%). 47% of the E.C.G.s were abnormal. A change in clinical diagnosis occurred in 28% of cases and in patient management in 16%. A significant number of these changes were unwarranted, however. It is recommended that the E.C.G.s should be recorded by suitably trained nurses and reported by a specially trained general practitioner. Further education of general practitioners in the clinical use of the E.C.G. is required.     

The radiation bystander effect and its potential implications for human health

A long-held dogma in radiation biology has been that the biological effects of exposure to ionizing radiation occur as a result of damage in directly irradiated cells and that no effect would occur in neighboring unirradiated cells. This paradigm has been frequently challenged by reports of radiation effects in unirradiated or 'bystander' cells receiving signals from directly irradiated cells, an issue that may have substantial impact on radiation risk assessment and development of radiation-based therapies. Radiation-induced bystander effects have been shown in single-cell systems in vitro for an array of cancer relevant endpoints, and may trigger damage in more complex 3-D tissue systems. They may be mediated by soluble factors released by irradiated cells into the extracellular environment and/or by the passage of mediator molecules through gap-junction intercellular communication. To date, evidence that radiation-associated bystander or abscopal responses are effectual in vivo has been limited, but new data suggest that they may significantly affect tumor development in susceptible mouse models. Further understanding of how the signal/s is transmitted to unirradiated cells and tissues and how it provokes long-range and significant responses is crucial. By summarizing the existing evidence of radiation induced bystander-like effects in various systems with emphasis on in vivo findings, we will discuss the potential mechanisms involved in these observations and how effects in bystander cells contribute to uncertainties in assessing cancer risks associated with radiation exposure.     

Polymorphism of bovine beta-casein and its potential effect on human health

Proteins in bovine milk are a common source of bioactive peptides. The peptides are released by the digestion of caseins and whey proteins. In vitro the bioactive peptide beta-casomorphin 7 (BCM-7) is yielded by the successive gastrointestinal proteolytic digestion of bovine beta-casein variants A1 and B, but this was not seen in variant A2. In hydrolysed milk with variant A1 of beta-casein, BCM-7 level is 4-fold higher than in A2 milk. Variants A1 and A2 of beta-casein are common among many dairy cattle breeds. A1 is the most frequent in Holstein-Friesian (0.310-0.660), Ayrshire (0.432-0.720) and Red (0.710) cattle. In contrast, a high frequency of A2 is observed in Guernsey (0.880-0.970) and Jersey (0.490-0.721) cattle. BCM-7 may play a role in the aetiology of human diseases. Epidemiological evidence from New Zealand claims that consumption of beta-casein A1 is associated with higher national mortality rates from ischaemic heart disease. It seems that the populations that consume milk containing high levels of beta-casein A2 have a lower incidence of cardiovascular disease and type 1 diabetes. BCM-7 has also been suggested as a possible cause of sudden infant death syndrome. In addition, neurological disorders, such as autism and schizophrenia, seem to be associated with milk consumption and a higher level of BCM-7. Therefore, careful attention should be paid to that protein polymorphism, and deeper research is needed to verify the range and nature of its interactions with the human gastrointestinal tract and whole organism.     

Maintaining life and health by natural selection of protein molecules.

A concept for a life and health-preserving principle is presented, with reference to evolutionary, medical, and biochemical observations. Life comprises two basic phenomena: it unfolds over longer periods at the population level, and is sustained for the duration of individual life spans. The evolution of life within populations by means of natural selection of individuals is central to Darwin's theory of evolution. An important component of maintaining individual life is proposed here to be the natural selection of molecular components-the proteins, a process of preferred removal of denatured and old, synonymous with the selection of younger, functional molecules. The proteins of the cell are committed to fulfilling all the tasks programmed by the genome while continuously maintaining all appropriate cellular functions, including protecting the DNA. Physiological and environmental influences accelerate the breakdown of aged protein molecules, driving this renewal process so that the cell can maintain its protein stock at high-performance levels. The principle of selection makes the incredible dynamics of continual protein turnover, and hence not only the preservation of life, but the maintenance of health in individual beings, comprehensible. Arguments are presented to counter the hypothesis that protein breakdown is a stochastic, random process governed by first-order kinetics.     

A cumulative experience examining the effect of natural and synthetic antimicrobial peptides vs. Chlamydia trachomatis.

We tested the activity of 48 structurally diverse antimicrobial peptides against Chlamydia trachomatis, serovar L2. The peptides' activity against C. trachomatis, serovar L2 was measured in 48-h McCoy cell shell vial assays. Peptides of 16-20 amino acids were more active than larger peptides, such as defensins. Beta-sheet protegrins, as well as alpha-helical peptides such as novispirin (G-10) were equally active. Enantiomers were as active as native structures. Moderate-sized circular mini-defensins were less effective against C. trachomatis. Moderate-sized cationic peptides may be useful in microbicide preparations designed to prevent chlamydial infection.     

A comprehensive study of eco-friendly natural pigment and its applications

Actinomycetes, a large group of filamentous bacteria account for 70–80% of secondary metabolites available commercially. The present investigation was undertaken with an aim to identify and characterize pigment from actinomycetes. Actinomycetes were isolated from rhizosphere soil samples collected from different regions of Madhya Pradesh state. Out of 85 actinomycetes, only 5 actinomycetes showed pigment production and based on diffusible pigment production ability one actinomycete ARITM02 was selected. The extraction of pigment was done by solvent extraction method using methanol and purified by TLC and column chromatography. The pigment was characterized by UV–Vis spectroscopy which showed the lamda maximum of 277.44. FTIR spectroscopy suggested various functional groups like amino group, amide group, hydroxide, benzene and lactone group. The Mass spectroscopy and NMR spectroscopy showed that the molecular mass of pigment is 621.7 and molecular formula is C34H43N3O8. The pigment was also tested for Antimicrobial activity against broad spectrum human pathogens, antioxidant test and toxicity test for safe use as a natural colorant in cosmetic, food, pharmaceutical and textile industries. The conclusion of study suggested that this novel pigment could be a versatile natural, safe and multipurpose.     

A note onSaissetia oleae and its natural enemies in Iran

A cursory survey made in the Rudbar area and on the Caspian coast in Iran revealed that two species ofChalcidoidea, five species of Coccinellids, one Nitidulid and one Neuropteron attackedSaissetia oleae (Ol.). Of thesePullus sp. andScymnus sp. (Coccinellidae) were common and appeared to be important biological control agents.     

Oleandomycin and its natural and synthetic analogs. I. Dissociative ionization of oleandomycin and its derivatives

Regularities of dissociative ionization of compounds belonging to the oleandomycin group were studied. Mass spectra of oleandomycin and some of its derivatives including anhydrooleandomycin, oleandomycin chlorhydrine, desoleandomycin, oleandomycin oxide, trimethylsilyl and acetyl derivatives were analyzed comparatively. Directions of disintegration with breakage of the glycoside bonds, macrolactone and carbon cycles were detected. The data are useful in structural analysis of not described oleandomycin-related compounds formed during biosynthesis and isolation of the main product.     

A novel, specific interaction involving the Csk SH3 domain and its natural ligand.

C-terminal Src kinase (Csk) takes part in a highly specific, high affinity interaction via its Src homology 3 (SH3) domain with the proline-enriched tyrosine phosphatase PEP in hematopoietic cells. The solution structure of the Csk-SH3 domain in complex with a 25-residue peptide from the Pro/Glu/Ser/Thr-rich (PEST) domain of PEP reveals the basis for this specific peptide recognition motif involving an SH3 domain. Three residues, Ala 40, Thr 42 and Lys 43, in the SH3 domain of Csk specifically recognize two hydrophobic residues, Ile 625 and Val 626, in the proline-rich sequence of the PEST domain of PEP. These two residues are C-terminal to the conventional proline-rich SH3 domain recognition sequence of PEP. This interaction is required in addition to the classic polyproline helix (PPII) recognition by the Csk-SH3 domain for the association between Csk and PEP in vivo. NMR relaxation analysis suggests that Csk-SH3 has different dynamic properties in the various subsites important for peptide recognition.     

Constipating and spasmolytic effects of Khat (Catha edulis Forsk) in experimental animals.

The constipating and spasmolytic effects of Catha edulis Forsk (Khat) were investigated in whole mice and on isolated guinea pig ileum. D-amphetamine was employed in both experiments for comparison. The total distance travelled (expressed in percentage) by charcoal suspension in the gastrointestinal tract of mice was determined before and after khat administration. The procedure was repeated with amphetamine and normal saline. The results were compared. Amplitudes of contraction were recorded with standard spasmogens, histamine and carbachol, in the presence and absence of khat extract of different concentrations. The same was done with amphetamine. Khat extract was observed to reduce the total distance travelled by charcoal suspension, comparable to D-amphetamine. The spasmogenic effects of both histamine and carbachol were observed to be antagonized by the khat extract in a concentration-dependent manner. The antispasmodic effect of khat extract was observed to be similar to that of D-amphetamine.     

The Matthew effect in health development.

A study was conducted examining the paradox that populations with a poor standard of health seem to achieve only meagre improvements over time, whereas those with a good standard of health seem to show continual, substantial improvement. The health states of 122 nations were measured by reference to their infant mortality in 1965 and the changes that occurred over the next 20 years. Countries with low infant mortality in 1965 (for example, Japan and East Germany) achieved substantial, further declines over the 20 years, whereas in countries such as Rwanda and Ethiopia infant mortality hardly declined at all or even increased (Ethiopia 165/1000 to 168/1000). In 48 countries for which data were available there was a close link between the change in health state of a people and the ratio of government expenditure on health and defence. As the ratio increased in favour of defence, so the improvement in health state of a people declined; the reverse was also true. At the primary care level disparity in uptake of care both among and within communities was associated with literacy and socioeconomic state, services inadvertently being aimed at those sections most likely to benefit. The forces that act to produce this setting of unequal care must be checked at both national and primary levels if we are to have "Health for All by the Year 2000."     

The effect of natural selection on enzymic catalysis.

The karyotype of Drosophila nasutoides reveals a very large autosome pair at the metaphase plate. The application of the C-banding technique shows that this chromosome is almost entirely heterochromatic and an isochromosome (Cordeiro et al., 1975). Examination of the DNA isolated from purified nuclei of D. nasutoides in neutral CsCl gradients reveals four major satellites. As much as 60% of the total DNA appears as satellites in the DNA from larval brains. The buoyant densities of the four satellites, designated as I through IV in the order of descending density, are 1.687, 1.682, 1.669 and 1.665 g/cm³, respectively. All four satellites show strand separations in alkaline CsCl gradients with the least separation in satellite III. Thermal denaturation studies with purified native satellites show that satellites I and IV consist of repeats of identical sequences, whereas satellites II and III show a large sequence variation between repeating units. As much as 10 to 24% base-pair mis-matching is observed in the reassociated satellite II. The sequence complexities obtained from DNA reassociation kinetics data are 5, 103, 2.3 × 10⁶ and 46 nucleotide pairs for the satellites I, II, III and IV, respectively. The complexity of satellite III is almost as large as that of Escherichia coli, when the reassociation rate is corrected according to the amount of mis-matching in this satellite. All four satellite sequences are localized in one chromosome (dot chromosome) according to in situ hybridizations to polytene chromosomes. The large heterochromatic chromosome seen at the metaphase plate appears as the dot chromosome after polytenization. Therefore, the large heterochromatic chromosome contains all four satellite DNA components.