Clinical and pharmacokinetic characteristics of intracavitary administration of pegylated liposomal encapsulated doxorubicin in dogs with splenic hemangiosarcoma

BACKGROUND: Canine splenic hemangiosarcoma (HSA) is a fatal malignancy, and most affected dogs die within a few months of diagnosis. Most dogs present with signs from tumor rupture, resulting in hemoabdomen and intra-abdominal dissemination. The abdomen is also the main site of disease recurrence. HYPOTHESIS: Intraperitoneal (IP) administration of doxorubicin will delay or prevent intra-abdominal tumor recurrence and prolong survival in dogs with HSA. ANIMALS: Fourteen dogs with splenic HSA. METHODS: A prospective, unmasked, uncontrolled clinical trial. After staging of disease status and splenectomy, pegylated liposomal encapsulated doxorubicin was administered intraperitoneally (1 mg/kg body weight) every 3 weeks for 4 cycles. All dogs were monitored for recurrence of HSA. Samples of plasma and abdominal fluid were collected for measurement of doxorubicin concentration and pharmacokinetic analysis. Nonlinear mixed-effect modeling was used to describe the pharmacokinetics of liposomal doxorubicin administered IP. RESULTS: All 14 dogs died, 12 because of HSA and 2 from other causes. Postmortem examination was performed on 12 dogs. All 12 dogs died because of HSA-related causes and had hepatic metastases and hemoabdomen. The IP-treated dogs had fewer serosal, mesenteric, and omental metastases than historical controls treated with systemic doxorubicin. Results of the postmortem examination and pharmacokinetic analysis confirmed that IP delivery of doxorubicin resulted in an effective drug concentration with a clearance comparable with that after i.v. delivery. CONCLUSIONS AND CLINICAL IMPORTANCE: IP pegylated liposomal encapsulated doxorubicin administration did not prevent intraabdominal recurrence of HSA in dogs.     

Biological Activities of Chickpea in Human Health (Cicer arietinum L.). A Review

Plant Foods for Human Nutrition - Chickpea is one of the most consumed legumes worldwide. Among their benefits are the high protein concentration that reflects not only at the nutritional level but...     

Mussel Shells,a Valuable Calcium Resource for the Pharmaceutical Industry

(1) Background: The mussel (Mytilus edulis, Mytilus galloprovincialis) is the most widespread lamellibranch mollusk, being fished on all coasts of the European seas. Mussels are also widely grown in Japan, China, and Spain, especially for food purposes. This paper shows an original technique for mussel shell processing for preparation of calcium salts, such as calcium levulinate. This process involves synthesis of calcium levulinate by treatment of Mytilus galloprovincialis shells with levulinic acid. The advantage of mussel shell utilization results in more straightforward qualitative composition. Thus, the weight of the mineral component lies with calcium carbonate, which can be used for extraction of pharmaceutical preparations. (2) Methods: Shell powder was first deproteinized by calcination, then the mineral part was treated with levulinic acid. The problem of shells generally resulting from the industrialization of marine molluscs creates enough shortcomings, if one only mentions storage and handling. One of the solutions proposed by us is the capitalization of calcium from shells in the pharmaceutical industry. (3) Results: The toxicity of calcium levulinate synthesized from the mussel shells was evaluated by the method known in the scientific literature as the Constantinescu phytobiological method (using wheat kernels, Triticum vulgare Mill). Acute toxicity of calcium levulinate was evaluated; the experiments showed the low toxicity of calcium levulinate. (4) Conclusion: The experimental results highlighted calcium as the predominant element in the composition of mussel shells, which strengthens the argument of capitalizing the shells as an important natural source of calcium.     

A Greener UV and Peroxide-Based Chemical Oxygen Demand Test

Water quality assessment typically includes the determination of chemical oxygen demand (COD) by oxidation of organic matter with Cr(VI) in an acidic medium followed by digestion. Unfortunately, the required reagents are harmful and the reaction times are rather long. We investigated earlier the use of H₂O₂ as a more environmentally friendly oxidizing agent to replace the hazardous chromates. In the present study, we have furthered this possibility by incorporating the use of H₂O₂ in the presence of UV light. A protocol has been devised and tested with standards and real samples that replaces toxic Cr(VI), halves the amount of silver sulfate required, and greatly reduces the necessary reaction time, thus yielding a faster and more environmentally sound method.     

Aboveground biomass,transpiration and water use efficiency in eucalypt plantation fertilized with KCl,NaCl and phonolite rock powder

Potassium has important physiological functions in eucalypt plantations, increasing their productivity when applied to soil via mineral fertilizers. There is interest in identifying alternative sources to KCl owing to its high cost and limited reserves. The aim of the study was to test the effect of replacing KCl with NaCl and phonolite rock powder. Two comparisons were made: (1) application of 283 kg ha^?1 of KCl compared with that of 2125 kg ha^?1 of phonolite rock powder (equivalent to 170 kg ha^?1 of K₂O in both treatments); (2) application of 139 kg ha^?1 of NaCl compared with that of 183 kg ha^?1 of KCl (equivalent to 2.33 kmol Na and K, respectively). Radial growth, soil water content, leaf water potential (Ψ), accumulated transpiration, stem volume and biomass increment, as well as water use efficiency (WUE) were evaluated. In the first comparison, both fertilizations presented equal values for all characteristics evaluated. In the second, the accumulated transpiration in trees fertilized with KCl was 17% higher than that in plants fertilized with NaCl. In contrast, the WUE was 20% higher in the trees fertilized with NaCl than in those fertilized with KCl, reflecting the lower water consumption for the same increment in stem volume and biomass. We conclude that phonolite rock powder and NaCl are possible substitutes for conventional K fertilization performed with KCl.

     

Chitosan-Based Films with 2-Aminothiophene Derivative: Formulation,Characterization and Potential Antifungal Activity

In this study, films of chitosan and 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile (6CN), a 2-aminothiophene derivative with great pharmacological potential, were prepared as a system for a topical formulation. 6CN-chitosan films were characterized by physicochemical analyses, such as Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray diffraction (XRD), and scanning electronic microscopy (SEM). Additionally, the antifungal potential of the films was evaluated in vitro against three species of Candida (C. albicans, C. tropicalis, and C. parapsilosis). The results of the FTIR and thermal analysis showed the incorporation of 6CN in the polymer matrix. In the diffractogram, the 6CN-chitosan films exhibited diffraction halos that were characteristic of amorphous structures, while the micrographs showed that 6CN particles were dispersed in the chitosan matrix, exhibiting pores and cracks on the film surface. In addition, the results of antifungal investigation demonstrated that 6CN-chitosan films were effective against Candida species showing potential for application as a new antifungal drug.     

The effects of GnRH and adrenergic agents on PRL and beta-endorphin secretion by porcine pituitary cells in vitro

The direct effects of alpha- and beta-adrenergic agents on PRL and beta-endorphin (beta-END) secretion in vitro by porcine pituitary cells have been investigated. Pituitary glands were obtained from mature gilts, which were ovariectomised (OVX) one month before slaughter. Ovariectomised gilts, assigned to four groups, were primed with: (1) vehicle (OVX); (2) and (3) oestradiol benzoate (EB; 2.5 mg/100 kg b.w.) at 30-36 h (OVX+EB I) and 60-66 h (OVX+EB II) before slaughter, respectively; and (4) progesterone (P4; 120 mg/100 kg b.w.) for 5 consecutive days before slaughter (OVX+P4). Isolated anterior pituitary cells were submitted to 3.5 h incubation in the presence of GnRH, alpha- and beta-adrenergic agonists [phenylephrine (PHEN) and isoproterenol (ISOP), respectively], or alpha- and beta-adrenergic blockers [phentolamine (PHENT) and propranolol (PROP), respectively]. The culture media were assayed for PRL (exp. I) and beta-endorphin-like immunoreactivity (beta-END-LI) (experiment II). In experiment I, GnRH did not influence PRL release by pituitary cells in all experimental groups. Some of tested doses of adrenergic agonists, PHEN and ISOP, increased PRL release from pituitary cells of OVX gilts, but not from those of OVX+EB I animals. In the OVX+EB II group, PHEN alone, but ISOP with PROP, potentiated PRL secretion by the cells. In OVX+P4 animals, PHEN alone or in combination with PHENT and also ISOP alone or with PROP enhanced PRL output from the cells. In experiment II, addition of GnRH increased beta-END-LI release from pituitary cells only in the OVX+EB II group. PHEN and PHENT potentiated beta-END-LI secretion by pituitary cells in OVX+EB II and OVX+P4 groups, while ISOP and PROP increased beta-END-LI secretion by the cells of OVX and OVX+EB II animals. In turn, in the OVX+EB I group, effect of PHENT and PROP on PRL secretion by pituitary cells was inhibitory. In conclusion, our results suggest that adrenergic agents can modulate PRL and beta-END secretion by porcine pituitary cells in a manner dependent on the hormonal status of gilts.     

Tick salivary gland extract-activated transmission of Borrelia afzelii spirochaetes

Saliva-activated transmission of Borrelia afzelii Canica, Nato, du Merle, Mazie, Baranton et Postic, 1993 was demonstrated using salivary gland extract (SGE) from Ixodes ricinus (L., 1758) ticks and C3H mice. Injection of Borrelia spirochaetes together with SGE increased the level of bacteraemia and accelerated the appearance of bacteria in the urinary bladder, compared with the injection of spirochaetes alone. More I. ricinus nymphs became infected when feeding on mice inoculated with B. afzelii plus SGE. Analysis of cytokines produced by cells of draining lymph nodes from SGE-treated mice showed a suppression of proinflammatory cytokines IFN-gamma, IL-6 and GM-CSF following a transient upregulation in comparison with the control mice infected without SGE.     

Improvements in somatic embryogenesis protocol in Feijoa (Acca sellowiana (Berg) Burret): Induction,conversion and synthetic seeds

Pineapple guava (Acca sellowiana) syn. Feijoa sellowiana, a Brazilian indigenous Myrtaceae is under domestication in South Brazil. Previous works showed that this species is responsive to somatic embryogenesis and recalcitrant to conventional methods of clonal propagation. In the present work it was evaluated the role of components of culture medium in the induction and development of somatic embryos. The technology of synthetic seeds was also evaluated. Zygotic embryos were inoculated in LPm medium supplemented with 8 mM glutamic acid and 8 mM l-glutamine, 2,4-dichlophenoxiacetic acid (20 μM) and myo-inositol. For conversion of somatic embryos and synthetic seeds it was tested the effect of 6-benzylaminopurine and gibberellic acid combined or not with activated charcoal. The highest values for embryogenetic induction (100%) and number of somatic embryos/explant (113) were observed in the LPm medium supplemented with Glu (8 mM), and 2,4-D. The culture medium supplemented with BA (0.5 μM) and GA₃ (1 μM) and activated charcoal (1.5 g L⁻¹) enhanced the conversion of somatic embryos to plantlets. Pre-germinated somatic embryos encapsulated in sodium alginate with BA (0.5 μM) and GA₃ (1 μM) developed radicles. The use of synthetic seed was a requisite for the survival of plantlets.