Aqueous Allium sativum (garlic) extract ameliorated CdCl2- induced alterations in blood formation and spermatogenesis in albino rats

Purpose: To investigate the ameliorative effect of aqueous garlic extract (AGEx) on cadmium chloride (CdCl2-induced) alterations in the blood and testicles of rats. Methods: A total of 24 male rats (160 - 200 g), randomly assigned into 4 groups (A - D; n = 6), were used to investigate the claimed protective effect of AGEx on blood and spermatogenic tissues following CdCl2-intoxication in albino rats. The rats in Group A served as controls and were given 5 mg/mL of deionized water. Group B rats were given 300 mg/kg of AGEx. Group C rats were given 2 mg/kg of CdCl2. Rats in Group D first received 2 mg/kg of CdCl2, and 300 mg/kg of AGEx 2 h later. All treatments were done every 48 h for a period of six weeks. Results: CdCl2 administration to group C rats reduced (p < 0.05) haematocrit value (PCV), concentration of haemoglobin (Hb), red cells count (RBC), total leucocytes count (tWBC), eosinophil, neutrophil, testicular weights and sperm reserves; but elevated (p < 0.05) lymphocytes count compared with the controls. AGEx 300 mg/kg in group D rats significantly reversed (p < 0.05) the altered parameters compared with the controls. Conclusion: The results demonstrate that administration of aqueous Allium sativum (garlic) extract to male rats enhances spermatogenesis, and ameliorates testicular and haematological alterations induced by cadmium poisoning. Therefore, the spermatogenic principle in AGEx is a potential candidate for the clinical management of male infertility.

Descartes on fermentation in digestion: iatromechanism, analogy and teleology

Fermentation is a cornerstone phenomenon in Cartesian physiology, accounting for processes such as digestion or blood formation. I argue that the previously unrecognized conceptual tension between the terms ‘fermentation’ and ‘concoction’ reflects Descartes's efforts towards a novel, more thoroughly mechanistic theory of physiology, set up against both Galenism and chymistry. Similarities with chymistry as regards fermentation turn out either epistemologically superficial, or based on shared earlier sources. Descartes tentatively employs ‘fermentation’ as a less teleological alternative to ‘concoction’, later renouncing the explicit use of the term, possibly to avoid chymical overtones. However, his continued use of analogies with fermentative processes in the natural world and in winemaking, coupled with a strong ontological commitment (the stance that the physiological processes are actual fermentations), leads to a reintroduction of natural teleology in his medical system, which I argue may be understood in an Aristotelian sense of ‘simple necessity’. The paper reveals a more nuanced account of Cartesian fermentative medicine, delineating some of its tensions with regard to chymistry as they play out in the dynamics of fermentation and concoction, and linking the analogies to fermentation processes to the difficulties in erasing teleology altogether.

Role of the HOXA cluster in HSC emergence and blood cancer

Hematopoiesis, the process of blood formation, is controlled by a complex developmental program that involves intrinsic and extrinsic regulators. Blood formation is critical to normal embryonic development and during embryogenesis distinct waves of hematopoiesis have been defined that represent the emergence of hematopoietic stem or progenitor cells. The Class I family of homeobox (HOX) genes are also critical for normal embryonic development, whereby mutations are associated with malformations and deformity. Recently, members of the HOXA cluster (comprising 11 genes and non-coding RNA elements) have been associated with the emergence and maintenance of long-term repopulating HSCs. Previous studies identified a gradient of HOXA expression from high in HSCs to low in circulating peripheral cells, indicating their importance in maintaining blood cell numbers and differentiation state. Indeed, dysregulation of HOXA genes either directly or by genetic lesions of upstream regulators correlates with a malignant phenotype. This review discusses the role of the HOXA cluster in both HSC emergence and blood cancer formation highlighting the need for further research to identify specific roles of these master regulators in normal and malignant hematopoiesis.

RNA-binding proteins PCBP1 and PCBP2 are critical determinants of murine erythropoiesis

We have previously demonstrated that the two paralogous RNA binding protein, PCBP1 and PCBP2, are individually essential for mouse development: Pcbp1 -null embryos are peri-implantation lethal while Pcbp2 -null embryos lose viability at mid-gestation. Mid-gestation Pcbp2 −/− embryos revealed a complex phenotype that included loss of certain hematopoietic determinants. Whether PCBP2 directly contributes to erythropoietic differentiation and whether PCBP1 has a role in this process remained undetermined. Here we selectively inactivate the genes encoding these two RNA-binding proteins during differentiation of the erythroid lineage in the developing mouse embryo. Individual inactivation of either locus fails to impact viability or blood formation. However, combined inactivation of the two loci results in mid-gestational repression of erythroid/hematopoietic gene expression, loss of blood formation, and fetal demise. Orthogonal ex-vivo analyses of primary erythroid progenitors selectively depleted of these two RNA binding proteins revealed that they mediate a combination of overlapping and isoform-specific impacts on hematopoietic lineage transcriptome, impacting both mRNA representation and exon splicing. These data lead us to conclude that PCBP1 and PCBP2 mediate functions critical to differentiation of the erythroid lineage.

THE USE OF NEW IMMUNOMODULATORS AT SECONDARY IMMUNODEFICIENCY

В данной статье рассматривается использование нового иммуномодулятора у животных, страдающих вторичным иммунодефицитом за период последнего года. В исследованиях России и Китая в качестве новых иммуномодуляторов применялись Ganodermalucidum (Gl-PS) полисахариды и стимфорт на фоне введения циклофосфана. Иммуномодуляция играет важную роль в кроветворении. На мышах исследовали возможный механизм активации миелопоэза при миелосупрессии, вызванной циклофосфамидом. Показано, что иммуномодулятор обладает способностью корригировать количественный и субпопуляционный состав МЛ селезенки, структуру центральных и периферических органов лимфопоэза, эффекторные функции клеток иммунитета, нарушенные при введении цитостатика. В настоящем исследовании invivo и invitro обнаружили, что иммуномодуляторы избирательно связываются со стромальными клетками костного мозга, стимулирует секрецию гемопоэтических факторов роста и усиливают клоногенную активность гемопоэтических и стромальных клеток, способствуя гемопоэзу у мышей с миелосупрессией. This article reviews the use of a new immunomodulator in animals for secondary immunodeficiency in the past year. In a study in Russia and China, Ganoderma lucidum (Gl-PS) polysaccharides and stimforte were used as new immunomodulators against the background of cyclophosphamide administration. Immunomodulation plays an important role in blood formation. A possible mechanism of myelopoiesis activation in cyclophosphamide-induced myelosuppression was investigated in mice. It was shown that the immunomodulator has the ability to correct the quantitative and subpopulation composition of spleen ML, the structure of the central and peripheral organs of lymphopoiesis, the effector functions of immunity cells, impaired by the introduction of a cytostatic. In the present study, in vivo and in vitro, it was found that immunomodulators selectively bind to bone marrow stromal cells, stimulate the secretion of hematopoietic growth factors and enhance the clonogenic activity of hematopoietic and stromal cells, promoting hematopoiesis in mice with myelosuppression.

Semen and haematological responses of rabbit bucks administered oral folic acid

Some researchers have inferred that folic acid is necessary for reproduction and could enhance blood formation. Thus, a Completely Randomized Design Experiment (CRD) was conducted to evaluate the impact of oral administration of folic acid on the semen and haematological characteristics of New Zealand White rabbit bucks. The treatments designated treatment 1 (T1), treatment 2 (T2) and treatment 3 (T3) having 12 rabbits each were replicated 3 times with 4 rabbits per replicate. The ages of the 36 pre-pubertal rabbit bucks were between 2 to 3 months, and weighed approximately 2.56 kg. Three experimental diets were formulated to meet the nutrient requirements of rabbit bucks. Each rabbit buck on T1 were orally administered folic acid at 0.0 mg, T2 2.5mg folic acid and T3 5.0 mg folic, respectively. Data were collected for semen characteristics and haematology from the rabbit bucks. Data collected on different parameters were subjected to analysis of variance (ANOVA). Results showed that significant increases (p<0.05) were observed on libido, semen pH, spermatozoa progressive motility (67.40-80.20%), spermatozoa live proportion (83.01-94.12%), sperm concentration (112.24-133.80 x106/ml), total number of sperm per ejaculate (50.65-67.66 x106/ml), total viable sperm (291.58-496.69 x109/ml), normal sperm proportion (85.16-91.64%). Also, significant reductions (p<0.05) were observed on the percentage head abnormality of the spermatozoa (3.74-3.18), total abnormality (2.13-0.93), mid-piece abnormality (2.35-0.79), cytoplasmic abnormality (7.17-2.89), and total abnormality (14.84-8.35); while the haematological parameters such as haemoglobin (13.53-14.20g/dl), packed cell volume (33.00-34.96%), white blood cell (6.81-7.80 x103mm3) and the differential white blood cells improved significantly (p<0.05) following the oral administration of folic acids to the rabbit bucks. Thus, the oral administrations of folic acid at 5.0 mg per rabbit buck most significantly improved the semen characteristics, enhanced the overall spermatozoa morphology, reduced sperm cells abnormalities and also improved some haematological parameters of the rabbit bucks.

To the question of reticuloendotheliosis

The division of leukemias, which existed until recently, or according to the latest terminology of leukemia, into two groups - lymphadenoses and myeloses, respectively, two genera of leicopoietic tissue according to the doctrine of dualists, has undergone significant changes in recent years due to the desire of a number of authors to delimit monocytes from the lymphatic and myeloid series in the form of a third independent type of blood cell elements. The works of Gold man n'a, Aschoff'a, Kiyono, Landau, Mac Nee and others put forward the doctrine of the reticuloendothelial system, the cells of which are attributed to a number of common properties: the ability to deposit electronegative colloidal substances in themselves, the ability to phagocytosis, and the participation of cells of this systems, both in embryonic and in subsequent life, especially under pathological conditions, in blood formation. Aschoff's research. Kiuono, Paschkis'a and others have shown that blood monocytes are in close genetic relationship with histiocytes of the r.-e. systems.

Differential Effects of RASA3 Mutations on Hematopoiesis are Profoundly Influenced by Genetic Background and Molecular Variant

Studies of the severely pancytopenic scat mouse model first demonstrated the crucial role of RASA3, a dual RAS and RAP GTPase activating protein (GAP), in hematopoiesis. RASA3 is required for survival in utero; germline deletion is lethal at E12.5-13.5 due to severe hemorrhage and decreased fetal liver erythropoiesis. Conditional deletion in hematopoietic stem and progenitor cells (HSPCs) using Vav-Cre recapitulates the null phenotype demonstrating that RASA3 is required at the stem and progenitor level to maintain blood vessel development and integrity and effective blood production. In adults, bone marrow blood cell production and spleen stress erythropoiesis are suppressed significantly upon induction of RASA3 deficiency, leading to pancytopenia and death within two weeks. Notably, RASA3 missense mutations in mouse models scat (G125V) and hlb381 (H794L) show dramatically different hematopoietic consequences specific to both genetic background and molecular variant. Global transcriptomic studies in scat suggest potential targets to ameliorate disease progression.Author SummaryHematopoiesis is the process by which blood cells are formed. The individual must have a normal complement of red blood cells to prevent anemia, platelets to control bleeding, and white blood cells to maintain immune functions. All blood cells are derived from hematopoietic stem cells that differentiate into progenitor cells that then develop into mature circulating cells. We studied several mouse strains carrying different mutations in RASA3. We show that RASA3 is required at the earliest stages of blood formation, the stem and progenitor cells, and that the complement of genes other than RASA3, or the genetic background of the mutant strain, profoundly alters the overall effect on blood formation. Further, the molecular nature of the mutation in RASA3 also has a profound and independent effect on overall blood formation. One strain, designated scat, suffers cyclic anemia characterized by severe anemic crisis episodes interspersed with remissions where the anemia significantly improves. Comparison of scat crisis and remission hematopoietic stem and progenitor cells reveals striking differences in gene expression. Analyses of these expression differences provide clues to processes that potentially drive improvement of anemia in scat and provide new avenues to pursue in future studies to identify novel therapeutics for anemia.