Indirani Kanakasabapathy

Propylthiouracil attenuates acetaminophen-induced renal damage in the rat.

Background:  To date, there is no specific antidote to acetaminophen poisoning. Propylthiouracil (PTU) has been shown to be protective against acetaminophen (APAP)‐induced liver damage in rats; however, the nephroprotective effect of propylthiouracil has not been studied yet.

Agenesis of the left lobe of liver - A rare anomaly with associated hepatic arterial variations.

Congenital absence of the left lobe of liver is a rare anomaly and reported sparsely in literature (Belton and VanZandt, 1983; Kakitsubata et al., 1991; Aktan et al., 2001; Saigusa et al., 2001; Lee et al, 2004; Koh et al., 2008). As partial agenesis of the liver is clinically asymptomatic with normal liver function parameters, absence is usually noted incidentally at autopsy or surgery (Kakitsubata et al., 1991; Saigusa et al., 2001, Koh et al., 2008). Most of the cases reported so far have been detected only using radiological studies, such as computed tomography or ultrasonography ( Radin et al., 1987; Kakitsubata et al., 1991;Saigusa et al., 2001). During routine dissection of a 68-year-old male cadaver, we found complete agenesis of liver to the left of the falciform ligament i.e. Couinaud’s segments II and III. There were five separate nodules of liver tissue each of size about 1.5 cm 3 2.0 cm situated close to the porta hepatis; one of which was attached to the falciform ligament and another to the gall bladder (Fig. 1a). Each of the liver nodules received a separate branch from the left branch of portal vein and drained separately via small extrahepatic ducts into the left hepatic duct (Fig. 1b). Right lobe of the liver was abnormal in shape with a poorly defined inferior border. The caudate lobe was grossly enlarged and showed a tongue like hypertrophy of the caudate process. A thickened pale white band of connective tissue was seen to the left of the falciform ligament and a sample of it was processed for histology (Fig. 1a). Gross alteration in the hepatic arterial pattern was seen. The right hepatic artery arose as a branch from the superior mesenteric artery, posterior to the body of the pancreas and ascended posterior to the first part of duodenum. Here the artery was situated posterior to the common bile duct and the formation of portal vein. It continued in the free border of lesser omentum (posterior to and between the common bile duct and portal vein) to supply the right lobe of liver. There were two left hepatic arteries. One arose as a branch from the terminal part of left gastric artery. The other arose as a terminal branch of the common hepatic artery and ascended within the lesser omentum to supply the remaining portion of the left surgical lobe (segment IV). The common hepatic artery divided into left hepatic artery and gastroduodenal artery. The cystic artery arose as a branch from the gastroduodenal artery, ascended obliquely to the right, in front of the common bile duct to reach the visceral surface of the gall bladder (Fig. 1b). The gall bladder, cystic duct, left and right hepatic ducts, common hepatic duct, and common bile duct were present and of normal size. The portal vein divided into left and right branches of equal size at the porta hepatis (Fig. 1b). The portal vein received the left and right gastric veins. The right, middle and left hepatic veins were present and drained into the inferior vena cava. Sample specimens were taken from the (1) right lobe, (2) one of the accessory nodules, and (3) liver tissue at its junction with the suspected remnant of septum transversum (boxed area in Fig. 1a) and processed for Hematoxylin Eosin staining. There was no hepatic parenchymal abnormality in the right lobe and accessory hepatic nodules; however, the sinusoids were enlarged and congested suggesting cardiac arrest as the cause of death. The junction between the liver tissue and the remnant of septum transversum was abrupt. Histology of the suspected septum transversum showed dense connective tissue containing numerous tubular structures and a few blood vessels. These features suggest an arrested development of a portion of hepatic epithelial trabeculae in the septum transversum mesenchyme. Many recent studies (Rossi et al., 2001; Bezerra, 2002; Kolterud et al., 2004), have shown that liver development is based on reciprocal interactions between the ventral foregut endoderm and adjacent mesenchymal tissues. Bezerra (2002) reports how cells from the septum transversum and cardiac mesoderm work in concert to induce hepatic specification of endodermal cells through the coordinated production of specific bone morphogenetic proteins (BMP)

Motor Recovery after Transplantation of Bone Marrow Mesenchymal Stem Cells in Rat Models of Spinal Cord Injury

Background: Neuronal tissue has a limited potential to self-renew or get repaired after damage. Cell therapies using stem cells are promising approaches for the treatment of central nervous system (CNS) injuries. However, the clinical use of embryonic stem cells is limited by ethical concerns and other scientific consequences. Bone marrow mesenchymal stromal cells (BM-MSC) could represent an alternative source of stem cells for replacement therapy. Indeed, many studies have demonstrated that MSCs can give rise to neuronal cells as well as many tissue-specific cell phenotypes. Purpose: Motor recovery by transplantation of bone marrow MSCs in rat models of spinal cord injury (SCI). Methods: Bone marrow was collected from the femur of albino Wistar rats. MSCs were separated using the Ficoll-Paque density gradient method and cultured in Dulbecco’s Modified Eagle Medium supplemented with 20% fetal bovine serum. Cultured MSC was characterized by immunohistochemistry and flow cytometry and neuronal-induced cells were further characterized for neural markers. Cultured MSCs were transplanted into the experimentally injured spinal cord of Wistar rats. Control (injured, but without cell transplantation) and transplanted rats were followed up to 8 weeks, analyzed using the Basso, Beattie, Bresnahan (BBB) scale and electromyography (EMG) for behavioral and physiological status of the injured spinal cord. Finally, the tissue was evaluated histologically. Results: Rat MSCs expressed positivity for a panel of MSC markers CD29, CD54, CD90, CD73, and CD105, and negativity for hematopoietic markers CD34, CD14, and CD45. In vitro neuronal transdifferentiated MSCs express positivity for β III tubulin, MAP2, NF, NeuN, Nav1.1, oligodendrocyte (O4), and negativity for glial fibrillary acid protein. All the treated groups show promising hind-limb motor recovery BBB score, except the control group. There was increased EMG amplitude in treated groups as compared to the control group. Green fluorescent protein (GFP)-labeled MSC survived and differentiated into neurons in the injured spinal cord, which is responsible for functional recovery. Conclusion: Our results demonstrate that BM-MSC has the potential to repair the injured cord in rat models of SCI. Thus, BM-MSC appears to be a promising candidate for cell-based therapy in CNS injury.

Globose basal cells for spinal cord regeneration

Spinal cord injury (SCI) is a devastating condition with loss of motor and sensory functions below the injury level. Cell based therapies are experimented in pre-clinical studies around the world. Neural stem cells are located intra-cranially in subventricular zone and hippocampus which are highly invasive sources. The olfactory epithelium is a neurogenic tissue where neurogenesis takes place throughout the adult life by a population of stem/progenitor cells. Easily accessible olfactory neuroepithelial stem/progenitor cells are an attractive cell source for transplantation in SCI. Globose basal cells (GBCs) were isolated from rat olfactory epithelium, characterized by flow cytometry and immunohistochemically. These cells were further studied for neurosphere formation and neuronal induction. T10 laminectomy was done to create drop-weight SCI in rats. On the 9th day following SCI, 5 × 105 cells were transplanted into injured rat spinal cord. The outcome of transplantation was assessed by the Basso, Beattie and Bresnahan (BBB) locomotor rating scale, motor evoked potential and histological observation. GBCs expressed neural stem cell markers nestin, SOX2, NCAM and also mesenchymal stem cell markers (CD29, CD54, CD90, CD73, CD105). These cells formed neurosphere, a culture characteristics of NSCs and on induction, differentiated cells expressed neuronal markers βIII tubulin, microtubule-associated protein 2, neuronal nuclei, and neurofilament. GBCs transplanted rats exhibited hindlimb motor recovery as confirmed by BBB score and gastrocnemius muscle electromyography amplitude was increased compared to controls. Green fluorescent protein labelled GBCs survived around the injury epicenter and differentiated into βIII tubulin-immunoreactive neuron-like cells. GBCs could be an alternative to NSCs from an accessible source for autologous neurotransplantation after SCI without ethical issues.

Bilateral Nephromegaly, Hepatomegaly and Retroaortic Left Renal Vein in a Patient with Aplastic Anaemia: An Unusual Presentation

Abstract This paper reports on a rare picture of hepatomegaly and bilateral nephromegaly along with retroaortic left renal vein which were noticed in a seventeen-year old male cadaver during routine dissection. The patient had been diagnosed with very severe aplastic anemia and treated with thymogam. He had received multiple transfusions and eventually died of septicaemic shock. Histological study of tissue samples of liver revealed portal canal fibrosis, bridging fibrosis, venous congestion, sinusoidal dilatation, hypertrophied Kupffer cells loaded with pigments, while kidney sections showed venous congestion without any major structural abnormality. From these observations we conclude that the patient had developed cardiac failure during the course of his ailment. We also concluded that the bilateral nephromegaly noted on routine dissection could be due to an underlying leukemic or myelodysplastic disorder whose presence is masked both clinically and diagnostically by the severe aplastic anaemia. The retroaortic course of the left renal vein was considered to be an incidental finding as no changes were noted solely on the left kidney though it has a possibility of causing retroaortic renal vein hypertension as co-morbidity.