Myeloid progenitor cells in the circulation of patients with myelofibrosis and other myeloproliferative disorders

We have measured the numbers of myeloid progenitor cells in the circulation of patients with myelofibrosis (MF) and other myeloproliferative disorders. In general, progenitor cell numbers were increased in the circulation of patients with MF compared with controls. The mean increases were 9-fold for the multilineage progenitor cells (CFU-GEMM), 13-fold for the erythroid progenitor cells (BFU-E), 37-fold for the granulocyte-macrophage progenitor cells (CFU-GM) and 167-fold for the megakaryocyte progenitors (CFU-MK). Splenectomized patients generally had reduced numbers of circulating progenitor cells. In the CFU-MK assay, mature megakaryocytes cultured from patients with MF regularly showed large vacuoles in the nucleus and cytoplasm, unlike control cells. The increased colony formation in patients with MK, involving especially CFU-MK colonies, is consistent with the hypothesis that MF is a primary myeloproliferative disorder in which a megakaryocyte-derived factor predisposes to the formation of marrow fibrosis.     

Assessment of aldehyde dehydrogenase in viable cells

Cytosolic aldehyde dehydrogenase (ALDH), an enzyme responsible for oxidizing intracellular aldehydes, has an important role in ethanol, vitamin A, and cyclophosphamide metabolism. High expression of this enzyme in primitive stem cells from multiple tissues, including bone marrow and intestine, appears to be an important mechanism by which these cells are resistant to cyclophosphamide. However, although hematopoietic stem cells (HSC) express high levels of cytosolic ALDH, isolating viable HSC by their ALDH expression has not been possible because ALDH is an intracellular protein. We found that a fluorescent aldehyde, dansyl aminoacetaldehyde (DAAA), could be used in flow cytometry experiments to isolate viable mouse and human cells based on their ALDH content. The level of dansyl fluorescence exhibited by cells after incubation with DAAA paralleled cytosolic ALDH levels determined by Western blotting and the sensitivity of the cells to cyclophosphamide. Moreover, DAAA appeared to be a more sensitive means of assessing cytosolic ALDH levels than Western blotting. Bone marrow progenitors treated with DAAA proliferated normally. Furthermore, marrow cells expressing high levels of dansyl fluorescence after incubation with DAAA were enriched for hematopoietic progenitors. The ability to isolate viable cells that express high levels of cytosolic ALDH could be an important component of methodology for identifying and purifying HSC and for studying cyclophosphamide-resistant tumor cell populations.     

Synergistic effect of aqueous extract of Telfaria occidentalis on the biological activities of artesunate in Plasmodium berghei infected mice

Background

Resistance to most antimalarial drugs has encouraged the use of herbal preparations along with prescribed orthodox drugs.

Objective

To investigate effect of co-administration of aqueous extract of T. occidentalis leaves; commonly used as antimalarial and haematinic agent in Nigeria and artesunate using P. berghei animal model.

Methods

In vivo curative antiplasmodial effect of T. occidentalis (200mg/kg) alone and combination with artesunate (2mg/kg) were evaluated using albino mice infected with 10⁶ parasitized erythrocytes of P. berghei intraperitoneally. The haematological parameters: haemoglobin level, red blood cells and white blood cells and packed cell volume were monitored using standard methods.

Results

Aqueous extract of T. occidentalis, artesunate and the combination gave 72.17±4.07%, 70.43± 4.27% and 85.43±3.65% reduction in parasitaemia after 48hours respectively. A significant enhancement of the PCV was obtained with the coadministration of artesunate and aqueous extract (p< 0.01). Similar trends were also observed with heamatological parameters at 72hours of administration.

Conclusion

This study revealed a synergistic effect of the co-administration on parasite clearance rate of P. berghei infection in mice, with a significant enhancement of haematological parameters within 48 hours of administration. This indicates a rapid rate of recovery from plasmodial infections with the co-administration.     

Antioxidant enzymes activity,lipid peroxidation,oxidative damage in the testis and epididymis,and steroidogenesis in rats after co‐exposure to atrazine and ethanol

Concomitant alcohol use and exposure to xenobiotics can adversely affect gonadal functions. This study investigated the oxidative status of the testis and epididymis and steroidogenesis of rats co‐exposed to ethanol (EtoH, 5 mg kg^?1 b.wt.) and atrazine (ATZ, 50, 100, 300 mg kg^?1 b.wt.) for 3 weeks. The activities of catalase, superoxide dismutase, glutathione peroxidase, as well as the concentrations of glutathione and malondialdehyde, as indicators of oxidative stress were measured in the homogenates of the testis and epididymis. Testosterone and cholesterol concentrations as well as 17β‐hydroxysteroid dehydrogenase (17β‐HSD) activity were assayed in the plasma and testis respectively. After the administration of EtoH alone, or in combination with different doses of ATZ, oxidative damage as evident by malondialdehyde level was not observed in both the testis and epididymis. The combine exposure group showed dose‐dependent decrease in plasma testosterone and testis cholesterol level and increase in testis 17β‐HSD activity compared to the EtoH group. Furthermore, the testes and epididymis of the EtoH‐exposed rats treated with high dose of ATZ had severe histopathological damage. Therefore, ATZ‐exposed alcohol‐treated rats have histological damage of the testis and epididymis and lower testosterone level than EtoH‐treated rats.     

Analysis of Risk Factors for Gunshot Wound Infection in a Nigerian Civilian Trauma Setting

Background

Survivors of firearm injury are at risk of wound infection. On average, civilian gunshot wound infection rates in developing countries are relatively high and almost on a par with infection rates in war trauma settings. Overall, there are limited data on civilian gunshot wound infection and its predisposing factors. The aim of this study was to determine the risk factors for gunshot wound infection in a civilian trauma setting of a developing nation.

Materials and method

This was a retrospective analysis of data on the entire patients who presented in Federal Teaching Hospital Abakaliki with firearm injury from January 2005 to December 2014.

Results

There were 196 patients, and wound infection was a complication in 58 (29.6 %) of them. The significant factors for high wound infection rate in univariate analysis were perforating wound (p < 0.001), high velocity injury (p < 0.001), haematocrit <30 % (p < 0.001), presence of fracture (p < 0.001), hollow viscus injury (p < 0.001) and injury to hospital arrival interval later than 6 h (p < 0.014). Anatomical site of injury correlated with infection rate (p < 0.001), highest rate (40.6 %) in lower extremity and least (9.1 %) in head and neck wounds. Multivariate logistic regression analysis identified haematocrit (p < 0.001), perforating wound (p < 0.021), presence of fracture (p < 0.043) and hollow viscus injury (p < 0.039) as independent predictors of gunshot wound infection.

Conclusion

The independent predictors of infection identified in this study call for judicious replacement of blood loss and high priority accorded to perforating wound, fractures and hollow viscus injury in interventions aimed at reducing gunshot wound infection rate.

     

Pyogenic Liver Abscess Following Pancreaticoduodenectomy: Risk Factors,Treatment, and Long-Term Outcome

Background

Pancreaticoduodenectomy (PD) remains a challenging operation with a 40 % postoperative complication rate. Pyogenic liver abscess (PLA) is an uncommon complication following PD with little information on its incidence or treatment. This study was done to examine the incidence, risk factors, treatment, and long-term outcome of PLA after PD.

Methods

We retrospectively reviewed 1,189 patients undergoing PD (N?=?839) or distal pancreatectomy (DP) (N?=?350) at a single institution over a 14-year period (January 1, 1994–January 1, 2008). Pancreatic databases (PD and DP) were queried for postoperative complications and cross-checked through a hospital-wide database using ICD-9 codes 572.0 (PLA) and 006.3 (amebic liver abscess) as primary or secondary diagnoses. No PLA occurred following DP. Twenty-two patients (2.6 %) developed PLA following PD. These 22 patients were matched (1:3) for age, gender, year of operation, and indication for surgery with 66 patients without PLA following PD.

Results

PLA occurred in 2.6 % (22/839) of patients following PD, with 13 patients (59.1 %) having a solitary abscess and 9 (40.9 %) multiple abscesses. Treatment involved antibiotics and percutaneous drainage (N?=?15, 68.2 %) or antibiotics alone (N?=?7, 31.8 %) with a mean hospital stay of 12 days. No patient required surgical drainage, two abscesses recurred, and all subsequently resolved. Three patients (14 %) died related to PLA. Postoperatively, patients with biliary fistula (13.6 vs. 0 %, p?=?0.014) or who required reoperation (18.2 vs. 1.5 %, p?=?0.013) had a significantly higher rate of PLA than matched controls. Long-term follow-up showed equivalent 1-year (79 vs.74 %), 2-year (50 vs. 57 %), and 3-year (38 vs. 33 %) survival rates and hepatic function between patients with PLA and matched controls.

Conclusions

Postoperative biliary fistula and need for reoperation are risk factors for PLA following PD. Antibiotics and selective percutaneous drainage was effective in 86 % of patients with no adverse effects on long-term hepatic function or survival.     

Separation of cholera enterotoxin-induced mucus secretion from electrolyte secretion in rabbit ileum by acetazolamide, colchicine, cycloheximide, cytochalasin B and indomethacin

In vivo rabbit ileal loops were prepared and inoculated with purified cholera enterotoxin (CT). After a lag period of about 1 h there was persistent stimulation of water and electrolyte secretion and a transient stimulation of mucus secretion into the luminal fluid. Repeated intraluminal inoculation of prostaglandin E1 (PGE1) caused a pattern of water, electrolyte and mucus secretion which was qualitatively the same as that following CT, except that no lag period was observed. Doses of the protein synthesis inhibitor, cycloheximide, the microtubule disrupter, colchicine, and the microfilament disrupter, cytochalasin B, were found that inhibited CT-induced mucus secretion but not water and electrolyte secretion. The carbonic anhydrase inhibitor, acetazolamide, inhibited CT-induced water and electrolyte secretion without inhibiting the mucus secreted over a 5-hour test period. Thus a variety of agents can be used to demonstrate a separation of intestinal water and electrolyte secretion from mucus secretion. The prostaglandin synthesis inhibitor, indomethacin, also inhibited CT-induced water, electrolyte and mucus secretion, but no dose of this agent was found that completely separated the water and electrolyte from the mucus secretion.