A Case Report of Porphyria Variegata Management in the Emergency Department

Background: Porphyria variegata (VP) is one of the hepatic porphyrias that results from the deficiency of protoporphyrinogen oxidase, an enzyme in the heme synthesis pathway. The name porphyria variegata refers to its many presentations, which include various neuropsychiatric and cutaneous manifestations. Emergency department (ED) presentations due to VP are most commonly neuropathic abdominal pain. Case Report: We present the case of a 57-year-old woman presenting to an ED with abdominal pain consistent with prior VP attacks. In addition to analgesics and supportive care, infusion of intravenous dextrose resulted in improvement in her symptoms. Conclusion: Intravenous dextrose and heme administration remain the first-line treatment for abdominal pain attributable to known acute hepatic porphyria attacks. Recently, the mechanism of action of carbohydrates in treating porphyria has been elucidated. Current information on this illness and ED management are discussed.     

Production and purification of an active CRM197 in Pichia pastoris and its immunological characterization using a Vi-typhoid antigen vaccine

CRM197 is a commonly used glycoconjugate carrier that improves the immunogenicity of vaccines, particularly in infants. Despite the advantages of this diphtheria toxoid mutant, low yields, production in inclusion bodies, and the requirement for specific growth conditions have limited the breadth of successful recombinant protein expression platforms available for its expression. We evaluated Pichia pastoris as a production host, using the methanol inducible AOX1 promoter and a modified α-mating factor signal peptide for secretion into the supernatant. Final purified yields >100 mg L⁻¹ culture were achieved when produced in a bioreactor, which is equivalent to the productivity obtained from bioprocesses using the native Corynebacterium diphtheriae host. Recombinant CRM197 was purified to ≥95% homogeneity and showed the expected endonuclease activity. Furthermore, mice immunized with a Salmonella enterica serovar Typhi capsular Vi antigen conjugated to our recombinant CRM197 showed greater than 5-fold increase in immune response. Overall, the results demonstrate that Pichia pastoris is a suitable expression host for the production of high quality CRM197 for vaccine applications.     

Polarity of extracts and fractions of four Combretum (Combretaceae) species used to treat infections and gastrointestinal disorders in southern African traditional medicine has a major effect on different relevant in vitro activities

Ethnopharmacological importance

Gastrointestinal disorders and infections are the major pathoaetiologies of diarrhoea causing many problems in human health and animal production. Many Combretum species are used in traditional medicine to treat infectious diseases including diarrhoea and many other ailments by rural people in Africa and Asia. Much of the work done to date on this genus was on the non-polar or intermediate polarity components. Some parameters that may cause diarrhoea and the evaluation of more polar extracts have apparently not been investigated.

Aims

The polar components were extracted and fractionated by solvent–solvent fractionation to yield fractions with different polarities. The activity of these fractions on different parameters that could be involved in factors associated with diarrhoea was investigated. The cytotoxic activities of the extracts were also determined to evaluate the potential of these extracts to combat diarrhoea in production animals.

Materials and methods

Phenolic-enriched leaf extracts of Combretum bracteosum (COB), Combretum padoides (COP), Combretum vendae (COV) and Combretum woodii (COW) were obtained by extracting with a mixture of 70% acetone acidified with 1% HCl and n-hexane. Acetone was removed from a portion of the 70% acetone extract and it was sequentially treated by solvent–solvent fractionation with dichloromethane, ethyl acetate, and butanol to yield fractions with a large variation in polarity. The phenolic constituents of the extracts and fractions were determined using standard procedures The antioxidant activities were determined using the 2,2-diphenyl-1-picrylhydrazyl (DPPH); 2,2′-azino-bis (3-ethylbenzothiazoline)-6-sulphonic acid (ABTS⁺) radical scavenging, ferric reducing antioxidant power (FRAP) methods and lipid peroxidation inhibitory capacity standard methods. The ferric reducing antioxidant activities of the fractions were also determined. The minimum inhibitory concentrations (MICs) of the crude extracts and fractions against four bacterial and three fungal strains were assessed with a microplate serial dilution method. Cyclooxygenase (COX) and lipoxygenase (LOX) enzyme inhibitory assays and cytotoxicity studies against Vero cells were also carried out.

Result

Some of the fractions had much higher antioxidant activity than the positive controls. The average EC₅₀ values of the extracts for the DPPH and ABTS antioxidant assays were 0.21–12 µg/ml (COP), 0.25–16 µg/ml (COV), 0.33–9.41 µg/ml (COW) and 4.97–85 µg/ml (COB) respectively while the mean EC₅₀ values for the positive controls ascorbic acid and trolox were 1.28–1.51 and 1.02–1.19 µg/ml respectively. All the crude extracts inhibited lipid peroxidation of linoleic acid by more than 80% at a concentration of 64 µg/ml. COP had the highest antibacterial activity with MICs ranging between 19–2500 µg/ml, followed by COV with MICs ranging between 39–625 µg/ml; COW and COB had similar MICs ranging between 39–2500 µg/ml. COP also had the highest antifungal activity with MICs between 19–625 µg/ml. The MIC for COW and COV ranged from 19 to 1250 µg/ml. COB had the lowest antifungal activity (MIC values were between 39 and 625 µg/ml). In general non-polar fractions had a high antimicrobial activity and polar fractions had a high antioxidant activity. The extracts had no activity against COX 1 and 2 enzymes in the anti-inflammatory assay but had good lipoxygenase inhibition. The crude extracts had high concentration of hydrolysable tannin (gallotannin). A good correlation (R²= 0.99) was found between the antioxidant activity and total tannin content indicating that, gallotannins may be responsible for the antioxidant activity.

Conclusion

The results obtained in this study with more polar extracts indicate that the use of extracts of these plant species as antidiarrhoeal agents may have a scientific basis. The extractant used here extracted a much higher percentage of the phytochemicals than acetone. It was better for isolating antioxidant compounds (polar) but not good for isolating antimicrobial compounds (non-polar) from the same species compared to acetone, ethyl acetate, dichloromethane, and hexane.     

Perioperative infusions in paediatric patients: rationale for using Ringer-lactate solution with low dextrose concentration

To assess the usefulness of Ringer-lactate solution with 0.9% dextrose, fluid therapy during surgery in paediatric patients was reviewed. From the literature, the need for intravenous (i.v.) infusion and water could be established. The need for sodium was also evident and use of normonatraemic i.v. solutions should be recommended to avoid hyponatraemia. Little data were found about the value of the other electrolytes. Dextrose requirements have been the subject of debate for the last two decades. The choice of dextrose concentration is a compromise between avoiding hypoglycaemia and hyperglycaemia. Four clinical trials assessing the use of Ringer-lactate solution with 0.9 or 1% dextrose in paediatric patients suggest that it is appropriate for routine infusion in paediatric patients during the perioperative period. However, fluid therapy during surgery has rarely been studied, probably because it is inexpensive, rarely leads to problems and is used in very different clinical settings. Development of consensus clinical guidelines on the use of electrolyte infusions in paediatric surgery would be helpful.     

Involvement of Src kinases and PLCgamma2 in clot retraction

The integrin alpha(IIb)beta(3) plays a critical role in mediating clot retraction by platelets which is important in vivo in consolidating thrombus formation. Actin-myosin interaction is essential for clot retraction. In the present study, we demonstrate that the structurally distinct Src kinase inhibitors, PP2 and PD173952, significantly reduced the rate of clot retraction, but did not prevent it reaching completion. This effect was accompanied by abolition of alpha(IIb)beta(3)-dependent protein tyrosine phosphorylation, including PLCgamma2. A role for PLCgamma2 in mediating clot retraction was demonstrated using PLCgamma2-deficient murine platelets. Furthermore, platelet adhesion to fibrinogen leads to MLC phosphorylation through a pathway that is inhibited by PP2 and by the PLC inhibitor, U73122. These results demonstrate a partial role for Src kinase-dependent activation of PLCgamma2 and MLC phosphorylation in mediating clot retraction downstream of integrin alpha(IIb)beta(3).     

Prospective Study of Systemic Yttrium-90 Elution during Radioembolization of Hepatic Metastases

PurposeTo evaluate total blood radioactivity (BR) after SIR-Spheres yttrium-90 (⁹⁰Y) radioembolization and differences in BR based on delivery method.Materials and MethodsTwenty participants with hepatic metastases undergoing first radioembolization were prospectively enrolled from December 2017 to June 2018. Blood samples were drawn at baseline and 0, 10, 20, 60, and 120 minutes after ⁹⁰Y administration. BR was measured with a γ-counter and scaled by estimated blood volume. Percentage of instilled radioactivity in the bloodstream was calculated as area under the fitted curve, and differences between delivery methods were examined with nonparametric statistical tests.ResultsIn 10 participants, resin microspheres were instilled with 50% Isovue 300 diluted in saline solution in the D line, and 10 others were treated with dextrose 5% in water (D5W) in the D line. Median administered activities were 944 MBq (range, 746–1,993 MBq) and 1,213 MBq (range, 519–2,066 MBq), respectively. Fraction of ⁹⁰Y in blood was significantly higher with dilute contrast agent than with D5W (median, 0.5% of injected activity vs 0.2%; P = .001). Among all participants, the maximum activity delivered was 2,066 MBq, and a maximum of 1% of administered radioactivity was measured as free ⁹⁰Y in blood. Assuming these highest-case values and complete decay of all free ⁹⁰Y in bone, a dose to red marrow of 132.3 mGy was calculated by Organ Level INternal Dose Assessment/EXponential Modeling.ConclusionsBlood sampling after radioembolization allowed for estimation of the time–activity curve and BR. Delivery with 50% contrast agent in saline solution resulted in a significant increase in BR vs D5W, even though the total BR for both groups was nominal.     

Platelet‐rich plasma limits the nerve injury caused by 10% dextrose in the rabbit median nerve

Introduction: We evaluated the effect of platelet‐rich plasma (PRP) injection in a rabbit model of dextrose‐induced median nerve injury. Methods: New Zealand white rabbits (n = 15) were divided randomly into 3 groups. Three different regimens (group 1: 0.1 ml saline; group 2: 10% dextrose with PRP; group 3: 10% dextrose with saline) were injected within the carpal tunnel. Electrophysiological and histological findings were evaluated 12 weeks after the injection. Results: The mean median motor latency in group 3 was significantly longer than that in groups 1 and 2. The cross‐sectional area of the median nerve and subsynovial connective tissue thickness in group 3 were significantly larger than those in groups 1 and 2. Conclusions: PRP injection may be effective in controlling median nerve injury, as demonstrated by improvement in electrophysiological and histological findings 12 weeks after dextrose injection. Muscle Nerve 49 : 56–60, 2014     

Antimicrobial activity and chemical composition of Mentha pulegium L. essential oil

ETHNOPHARMACOLOGICAL RELEVANCE: The flowering aerial parts of Mentha pulegium L. (Labiatae) has been traditionally used for its antiseptic properties for treatment of infectious diseases. AIM OF THE STUDY: In order to validate its antiseptic properties with respect to traditional uses, we have screened the antimicrobial activity of flowering aerial parts of Mentha pulegium L. essential oil against different microorganisms. MATERIALS AND METHODS: This oil was obtained using hydrodistillation method and analyzed by GC and GC/MS. The antimicrobial activity was achieved using disc diffusion method and microbroth dilution assay. RESULTS: Analysis of the essential oil revealed the presence of piperitone (38.0%), piperitenone (33.0%), alpha-terpineol (4.7%), and pulegone (2.3%) as the major components. The results showed a significant activity against microorganisms especially Gram-positive bacteria with inhibition zones and minimal inhibitory concentration values in the range of 8-21mm and 0.25-4mul/ml, respectively, whereas the least susceptible were Gram-negative bacteria especially Escherichia coli. CONCLUSIONS: This investigation showed that the oil of Mentha pulegium L. has a potent antimicrobial activity and the Iranian Mentha pulegium L. oil belongs to piperitone/piperitenone type. Further research is required to evaluate the practical values of therapeutic applications.     

Dextrose in the banked blood products does not seem to affect the blood glucose levels in patients undergoing liver transplantation

AIM: Hyperglycemia commonly seen in liver transplantation (LT) has often been attributed to the dextrose in the storage solution of blood transfusion products. The purpose of the study is to compare the changes of the blood glucose levels in transfused and non-transfused patients during LT. METHODS: A retrospective study on 60 biliary pediatric patients and 16 adult patients undergoing LT was carried out. Transfused pediatric patients were included in Group Ⅰ (GⅠ), those not transfused in Group Ⅱ (GⅡ). Twelve adult patients were not given transfusion and assigned to Group Ⅲ(GⅢ); whereas, four adult patients who received massive transfusion were assigned to Group Ⅳ (GⅣ). The blood glucose levels, volume of blood transfused, and the volume of crystalloid infused were recorded, compared and analyzed. RESULTS: Results showed that the changes in blood glucose levels during LT for both non-transfused and minimally transfused pediatric groups and non-transfused and massively-transfused adult groups were almost the same. CONCLUSION: We conclude that blood transfusion does not cause significant changes in the blood glucose levels in this study.