Capybara Oil Improves Renal Pathophysiology and Inflammation in Obese Mice.

Obesity is an inflammatory disease associated with secondary diseases such as kidney disease, which can cause lipotoxicity, inflammation and loss of organ function. Polyunsaturated fatty acids act in the production of lipid mediators and have anti-inflammatory characteristics. In this work, the objective was to evaluate renal histopathology in obese mice and the effects of treatment with capybara oil (CO) (5000 mg/kg/day for 4 weeks). Parameters such as body mass, lipid profile, systolic blood pressure, urinary creatinine and protein excretion, structure and ultrastructure of the renal cortex, fibrosis, tissue inflammation and oxidative stress were analyzed. CO treatment in obese mice showed improvement in the lipid profile and reduction in systolic blood pressure levels, in addition to beneficial remodeling of the renal cortex. Our data demonstrated that CO decreased inflammation, oxidative stress and renal fibrosis, as evidenced by quantifying the expression of TNF-α, IL-10, CAT, SOD, α-SMA and TGF-ß. Although treatment with CO did not show improvement in renal function, ultrastructural analysis showed that the treatment was effective in restoring podocytes and pedicels, with restructuring of the glomerular filtration barrier. These results demonstrate, for the first time, that treatment with CO is effective in reducing kidney damage, being considered a promising treatment for obesity.

The obesity and nonalcoholic fatty liver disease mouse model revisited: Liver oxidative stress, hepatocyte apoptosis, and proliferation.

The study revisited the diet-induced obesity (DIO) mice and the nonalcoholic fatty liver disease (NAFLD) pathogenesis to serve as a translational model. Hepatic beta-oxidation pathways, lipogenesis, oxidative stress, hepatocyte apoptosis, and proliferation were investigated in obese mice. Three-month-old male mice were divided according to their diet for fifteen weeks, the control diet (C group, containing 10% energy from fat) and the high-fat diet (HF group, containing 50% energy from fat). Body weight (BW), liver mass, and steatosis were higher in the HF group than in the C group. Also, gene expression related to beta-oxidation and lipogenesis showed an adverse profile, and insulin and glucose signaling pathways were impaired in the HF group compared to the C group. As a result, steatosis was prevalent in the HF group but not in the C group. Furthermore, the pathways that generate NAFLD were negatively modulated by oxidative stress in the HF animals than in the C ones. The caspase 3 immunolabeled HF hepatocytes with increased gene and protein expressions related to apoptosis while proliferating cell nuclear antigen labeled C hepatocytes. In conclusion, the findings in the DIO mouse model reproduce the NAFLD profile relative to the human NAFLD's apoptosis, insulin signaling, lipogenesis, beta-oxidation, and oxidative stress. Therefore, the model is adequate for a translational perspective's morphological, biochemical, and molecular research on NAFLD.

Phosphodiesterase-5 inhibition improves bone regeneration at the early stages of ischemic osteonecrosis of the femoral head in rats.

Posttraumatic osteonecrosis of the femoral head (ONFH) affects patients at different ages and may lead to functional limitation and joint replacement, with total hip arthroplasty, which is a costly procedure. Proposed methods to optimize ischemic tissue regeneration have been reported. Phosphodiesterase-5 inhibitors act by inhibiting the degradation of guanosine 3',5'-cyclic monophosphate in the nitric oxide pathway, increasing its bioavailability and promoting vascular endothelial growth factor (VEGF)-mediated neovascular recruitment and the induction of tissue regeneration in the traumatized bone. Thirty male Sprague-Dawley rats (6 months old) were subjected to an experimental model of traumatic ONFH divided into two groups, according to the administration of 5 mg/kg sildenafil or water (control group). Rats were then killed at 7, 14, and 21 days. Histological (Goldner's trichrome), histochemical (periodic acid-Schiff [PAS]), and immunohistochemical (VEGF and osteopontin [OPN]) techniques were used to quantify bone and vascular responses. Higher levels of VEGF (p < 0.01) and OPN (p < 0.01) immunostaining in the epiphysis, the greater formation of osteoid tissue (p < 0.01 on Day 7; p < 0.05 on Day 14), and higher levels of PAS staining (p < 0.01 on Day 7) were observed in the sildenafil-treated group. The present study demonstrated that sildenafil optimized bone tissue regeneration by increasing VEGF signaling and OPN expression, with increased bone formation (osteoid and carbohydrate macromolecule deposition) in the early stages following traumatic ischemic insult. Thus, sildenafil treatment may improve the prognosis of patients with osteonecrosis.

Aliskiren Reduces the Adrenal Zona Glomerulosa Apoptosis and Autophagy in Wistar Rats with 2K1C Hypertension.

Hypertension is a disease classified as primary or secondary, manifested not only by elevation of blood pressure but also involved in structural and functional changes of target organs. Renal artery stenosis is a leading factor of secondary hypertension, and its progress is associated with overactivation of the renin-angiotensin-aldosterone system (RAAS). Aliskiren is a renin inhibiting drug that suppresses RAAS and culminates in decreased renin release, plasma angiotensin II concentration, and inhibition of aldosterone secretion. In this sense, the aim of the present study was to analyze the structural and ultrastructural morphophysiology of the adrenal glomerular zone, after treatment with aliskiren in Wistar rats with 2K1C hypertension. Parameters as structure and ultrastructure of the adrenal glomerular zone, cellular apoptosis, nuclear cell proliferation, and AT1 receptor expression were analyzed by immunostaining and electron microscopy. Our results showed that the hypertensive animals treated with aliskiren presented a reestablishment of AT1 receptor expression and decrease in apoptosis and autophagy. In addition, treatment with aliskiren improves the cell aspects in the adrenal glomerular zone, evidenced by ultrastructural analysis through preserved nuclei and well-developed mitochondria. Therefore, our evidence suggests that aliskiren has a beneficial effect on the adrenal glomerular zone remodeling in animals with renovascular hypertension.

Aliskiren improves renal morphophysiology and inflammation in Wistar rats with 2K1C renovascular hypertension.

Hypertension is characterized by persistent elevated blood pressure levels, one of the leading causes of death in the world. Renovascular hypertension represents the most common cause of secondary hypertension, and its progress is associated with overactivation of the renin angiotensin aldosterone system (RAAS), causing systemic and local changes. Aliskiren is a renin-inhibiting drug that optimizes RAAS suppression. In this sense, the objective of the present study was to analyze the morphophysiology of the left kidney in Wistar rats with renovascular hypertension after treatment with Aliskiren. Parameters such as systolic blood pressure, urinary creatinine and protein excretion, renal cortex structure and ultrastructure, fibrosis and tissue inflammation were analyzed. Our results showed that the hypertensive animals treated with Aliskiren presented a reestablishment of blood pressure, expression of renin, and renal function, as well as a remodeling of morphological alterations through the reduction of fibrosis. The treatment regulated the laminin expression and decreased pro-inflammatory cytokines, restoring the integrity of the glomerular filtration barrier. Therefore, our findings suggest that Aliskiren has a renoprotective effect acting on the improvement of the morphology, physiology and pathology of the renal cortex of animals with renovascular hypertension.

Time course of cardiomyopathy induced by doxorubicin in rats.

BACKGROUND: Doxorubicin (DOX)-related cardiotoxicity may expose cancer survivors to increased risk of cardiovascular morbidity and mortality. Here, we characterized the time course of DOX-induced cardiomyopathy in rats. METHODS: Sprague-Dawley male rats (12 wk old) received doxorubicin hydrochloride (1 mg/kg/d, ip) during 10 consecutive days and they were euthanized one (DOX1), two (DOX2) or four (DOX4) weeks after the last drug injection. Control group received NaCl 0.9% (ip). Hearts were mounted on a Langendorff perfusion system, left ventricle fragments were processed for microscopy and oxidative stress-related assays, and blood was collected for cardiac troponin I assay. RESULTS: All DOX-treated groups showed swollen and vacuolated cardiomyocytes with myofilaments disarray and mitochondrial damage. These changes were already evident after one week and became more pronounced after four weeks. Cardiac troponin I plasma levels were significantly increased in DOX1 and further increased in DOX4 compared to control group. Increased oxidative damage to lipids was observed in DOX1, and to proteins in DOX4. Glutathione peroxidase activity increased in DOX4. The morphological changes resulted in cardiac remodeling, including interstitial fibrosis, apoptosis and significant impairment of both contractile and relaxation function in DOX 4 compared to control group. Hearts from all animals displayed an early reduction in the responsiveness to norepinephrine. CONCLUSIONS: These findings support the view that DOX cardiotoxicity occurs in a "continuum", and as the hypothesis of an irreversible cardiac injury is being challenged, understanding the progression of morphological and functional changes caused by DOX may allow proper timing of initiation of prophylactic treatment.

Placental Inflammation and Fetal Injury in a Rare Zika Case Associated With Guillain-Barré Syndrome and Abortion.

Zika virus (ZIKV) is an emerging virus involved in recent outbreaks in Brazil. The association between the virus and Guillain-Barré syndrome (GBS) or congenital disorders has raised a worldwide concern. In this work, we investigated a rare Zika case, which was associated with GBS and spontaneous retained abortion. Using specific anti-ZIKV staining, the virus was identified in placenta (mainly in Hofbauer cells) and in several fetal tissues, such as brain, lungs, kidneys, skin and liver. Histological analyses of the placenta and fetal organs revealed different types of tissue abnormalities, which included inflammation, hemorrhage, edema and necrosis in placenta, as well as tissue disorganization in the fetus. Increased cellularity (Hofbauer cells and TCD8+ lymphocytes), expression of local pro-inflammatory cytokines such as IFN-γ and TNF-α, and other markers, such as RANTES/CCL5 and VEGFR2, supported placental inflammation and dysfunction. The commitment of the maternal-fetal link in association with fetal damage gave rise to a discussion regarding the influence of the maternal immunity toward the fetal development. Findings presented in this work may help understanding the ZIKV immunopathogenesis under the rare contexts of spontaneous abortions in association with GBS.

Capybara Oil Improves Hepatic Mitochondrial Dysfunction, Steatosis, and Inflammation in a Murine Model of Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is recognized as the most common cause of liver dysfunction worldwide and is commonly associated with obesity. Evidences suggest that NAFLD might be a mitochondrial disease, which contributes to the hepatic steatosis, oxidative stress, cytokine release, and cell death. Capybara oil (CO) is a rich source of polyunsaturated fatty acids (PUFA), which is known to improve inflammation and oxidative stress. In order to determine the effects of CO on NAFLD, C57Bl/6 mice were divided into 3 groups and fed a high-fat diet (HFD) (NAFLD group and NAFLD + CO group) or a control diet (CG group) during 16 weeks. The CO (1.5 g/kg/daily) was administered by gavage during the last 4 weeks of the diet protocol. We evaluated plasma liver enzymes, hepatic steatosis, and cytokine expression in liver as well as hepatocyte ultrastructural morphology and mitochondrial function. CO treatment suppressed hepatic steatosis, attenuated inflammatory response, and decreased plasma alanine aminotransferase (ALT) in mice with NAFLD. CO was also capable of restoring mitochondrial ultrastructure and function as well as balance superoxide dismutase and catalase levels. Our findings indicate that CO treatment has positive effects on NAFLD improving mitochondrial dysfunction, steatosis, acute inflammation, and oxidative stress.

Protective Effects of Micronized Purified Flavonoid Fraction (MPFF) on a Novel Experimental Model of Chronic Venous Hypertension.

OBJECTIVES: To assess protective effects of micronized purified flavonoid fraction (MPFF) on microcirculation in an original chronic model of hind limb venous hypertension with low blood flow in small animals. METHODS: Vein ligatures were performed on male hamsters, as follows: A-right femoral vein; A + B-right femoral vein and its right branch; A + C-right femoral vein and its left branch; A + B + C-right femoral and its right and left branches; D-external right iliac vein. In sham operated groups, similar vascular dissections were performed without ligatures. Superficial (epigastric) and central (jugular) venous pressure evaluations were made during a 10 week period. Hamsters subjected to A + B + C and D ligatures were selected for leukocyte rolling and sticking, functional capillary density (FCD), and venular and arteriolar diameter observations. D ligature was selected to evaluate pharmacological treatment efficacy. MPFF (100 mg/kg), concomitant active flavonoids of MPFF (diosmetin, hesperidin, linarin, and isorhoifolin) (10 mg/kg), diosmin (100 mg/kg) or drug vehicle were administered orally during 2 weeks before vein ligature and 6 weeks thereafter. RESULTS: A, A + B and A + C models maintained venous return through collaterals. From the 2nd to the 10th weeks after vein ligatures, A + B + C and D models elicited a progressive increase of superficial venous pressure (3.83 ± 0.65 vs. 8.56 ± 0.72 mmHg, p < .001 and 4.13 ± 0.65 vs. 9.35 ± 0.65 mmHg, p < .001, respectively) with significant changes to the microcirculation. As D model significantly increased superficial venous pressure without affecting central venous pressure, it was used to evaluate the long-term effects of treatment. Compared with vehicle, MPFF, concomitant active flavonoids of MPFF, and diosmin, significantly decreased leukocyte-endothelium interaction and prevented FCD reduction. Only MPFF significantly prevented venular enlargement as observed in the vehicle treated group. CONCLUSION: MPFF was more effective than diosmin in improving all microvascular variables. The superiority of MPFF over diosmin alone can be explained by the synergistic beneficial effects of the association between diosmin and active flavonoids of MPFF.

A combination of stereological methods, biochemistry and electron microscopy for the investigation of drug treatment effects in experimental animals.

Some chemotherapeutic agents used for breast cancer (BC) treatment can induce severe side effects in the ovarian tissue. The combination of cyclophosphamide and docetaxel (TC) is widely used for BC treatment; however, its late effects in the ovary are not completely understood. The main purpose of this study was to evaluate the structural and ultrastructural alterations in the ovarian stroma induced by TC treatment. Wistar rats were divided into two groups: a control group and a TC group. They were euthanized 5 months after the end of treatment, and their plasma and ovaries were collected. Important alterations were noted. The serum estradiol level was significantly reduced in the TC group compared with the control group. Additionally, the number of apoptotic nuclei was higher in the TC group. The role of the inflammatory response in the development of ovarian damage was investigated, and we found an increased number of mast cells and increased expression of TNF-α in the TC group. The involvement of fibrosis was also investigated. The results showed that the TC group had increased expression levels of TGF-ß1, collagen type I (col-I) and collagen type III (col-III) compared with the control group. Ultrastructural analysis revealed the presence of collagen fibrils in the treated group and illustrated that the ovarian tissue architecture was more disorganized in this group than in the control group. The results from this study are important in the study of chemotherapy-induced ovarian failure and provide further insight into the mechanisms involved in the development of this disease.

Gender-related differences in kidney of rats with chronic renal failure.

Chronic renal failure is characterized by adaptive mechanisms secondary to the loss of functioning nephrons. Clinical and experimental studies suggest participation of gender-related hormones on renal function and progression of chronic renal failure. We evaluated the effect of castration on renal alterations in male and female Wistar control rats and after 30 days of chronic renal failure (CRF) induced by 5/6 nephrectomy. The CRF male group showed higher proteinuria. Glomerular hypertrophy was similar among groups. Podocyte morphology showed disorders of foot processes and thickening of the basement membrane in the CRF male group. The CRF female group showed fewer alterations compared to males. Castration changed the profile in CRF male animals and the filtration barrier was preserved. CRF males showed the presence of alfa-smooth muscle actin suggesting an early prefibrotic event in this group. After castration this phenomenon was not observed. Noteworthy, in females, castration exacerbated the presence of alfa-smooth muscle actin. In summary, proteinuria was higher in males and appeared early in the course of CRF, probably contributing to fibrotic events. Data were influenced by gender suggesting that male sex hormones aggravate renal alterations.

In vitro and in vivo studies of an aqueous extract of Matricaria recutita (German chamomile) on the radiolabeling of blood constituents, on the morphology of red blood cells and on the biodistribution of the radiopharmaceutical sodium pertechnetate.

BACKGROUND: Natural products might alter the labeling of blood constituents with technetium-99m ((99m)Tc) and these results may be correlated with modifications of the shape of the red blood cells (RBC). The biodistribution of radiopharmaceuticals can be also altered. OBJECTIVE: This investigation aimed to determine biological effects of an aqueous extract of chamomile (CE). MATERIALS AND METHODS: To study the effect of the CE on the labeling of blood constituents with (99m)Tc, in vitro and in vivo assays were performed. The effect of the CE on the morphology of RBC was observed under light microscope. The images were acquired, processed, and the perimeter/area ratio of the RBC determined. To analyze the effect of the CE on biodistribution of the sodium pertechnetate (Na(99m)TcO4) in Wistar rats, these animals were treated or not with a CE. Na(99m)TcO4 was injected, the rats were sacrificed, the organs were removed, weighted and percentage of radioactivity/gram calculated. RESULT: In the in vitro experiment, the radioactivity on blood cells compartment and on insoluble fractions of plasma was diminished. The shape and the perimeter/area ratio of the RBC were altered in in vitro assays. An increase of the percentage of radioactivity of Na(99m)TcO4 was observed in stomach after in vivo treatment. CONCLUSION: These results could be due to substances of the CE or by the products of the metabolism of this extract in the animal organism. These findings are examples of drug interaction with a radiopharmaceutical, which could lead to misdiagnosis in clinical practice with unexpected consequences.

Therapeutic dose of Ginkgo biloba extract 761 may alter the urine excretion of Wistar rats

Wistar rats (n=20) were divided in two groups: G1 received 2 mg/kg of GBE (Ginkgo biloba extract 761), whereas G2 received the same volume of a sodium chloride solution (0.9%), both for 10 days. After a 7-day interval, the treatment was repeated for 8 days. Urine volume and food and water intake were measured daily during this protocol. Histological assessments were performed. No significant difference (p>0.05) was observed in food and water intake of animals during treatment with GBE. Animals who received GBE had a smaller urine volume and increase of weight with a significance difference (p<0.05) during the first and second exposure period. No histological alteration was observed in tissues, except for the kidney of the experimental group, which revealed a higher concentration of red cells in the glomerulus with a strong staining for Vascular Endothelial Growth Factor (VEGF). The introduction of GBE (therapeutic dose) in health rats may promote alterations in the physiology of the kidney, but no sufficient to modify the glomerulus architecture, including at ultra structural level (electron microscopy).

Upregulation of platelet (L)-arginine: nitric oxide pathway after exercise training in hypertension.

We investigated whether physical exercise can affect platelet L-arginine - nitric oxide pathway in spontaneously hypertensive rats (SHR). Sixteen male SHR and 16 Wistar Kyoto rats (WKY) were divided among exercise (EX) and sedentary (SED) groups. After 20 weeks of treadmill training, systolic blood pressure (mm Hg) was significantly lower in exercised spontaneously hypertensive rats (SHR/EX; 138 ± 8) than in sedentary spontaneously hypertensive rats (SHR/SED; 214 ± 9). Exercise significantly increased platelet L-arginine transport (pmol L-arginine·(10(9) cells)(-1)·min(-1)), assessed by incubation with L-[(3)H]-arginine, in both WKY (SED, 0.196 ± 0.054 compared with EX, 0.531 ± 0.052) and SHR (SED, 0.346 ± 0.076 compared with EX, 0.600 ± 0.049). Nitric oxide synthase (NOS) activity (pmol L-citrulline·(10(8) cells)(-1)), measured by the conversion of L-[(3)H]-arginine to L-[(3)H]-citrulline, was significantly increased in SHR/EX (0.072 ± 0.007) compared with SHR/SED (0.038 ± 0.007), but no changes were observed in WKY. The iNOS and eNOS protein levels assessed by Western blot were not affected by exercise. This upregulation of the platelet L-arginine-NO pathway may attenuate the risk of thromboembolic events, supporting the role of exercise in hypertension management.

Maternal high-fat intake predisposes nonalcoholic fatty liver disease in C57BL/6 offspring.

OBJECTIVE: This work aimed to verify the hypothesis that maternal intake of high-fat diet in critical periods of pregnancy and/or suckling period predisposes nonalcoholic fatty liver disease in adult C57BL/6 mice offspring. STUDY DESIGN: Male pups were divided into 5 groups: (1) SC, from standard chow-fed dams; (2) G, from high-fat chow (HF)-fed dams during the gestation (G) period; (3) L, from HF-fed dams during the lactation (L) period; (4) GL, from HF-fed dams during the gestation and lactation (GL) periods; and (5) GL/HF, from HF-fed dams during GL, maintaining an HF diet from postweaning to adulthood. We analyzed body mass, plasma blood, and liver structure. RESULTS: The G offspring showed insulin resistance and lower glucose transporter-2 expression. Hepatic steatosis was present in the G, L, GL, and mainly in GL/HF offspring. Sterol regulatory element-binding protein-1c expression was higher in G, GL, and GL/HF offspring. CONCLUSION: Programming by HF chow predisposes hepatic adverse remodeling in the liver of adult offspring.

Exercise training in doxorubicin-induced heart failure: effects on the L-arginine-NO pathway and vascular reactivity.

Heart failure (HF) is the end-stage of cardiovascular disease and is associated with a high incidence of thrombotic events. Nitric oxide (NO) mediates vasodilation and prevents platelet activation, providing an important antithrombotic effect. The aim of this study was to investigate the effects of aerobic training on survival, platelet L-arginine-NO pathway, and vasodilator properties in doxorubicin (DOX)-induced HF. Sprague Dawley rats were randomly assigned to saline/sedentary (SAL/SED), saline/exercise (SAL/EX), DOX/sedentary (DOX/SED), and DOX/exercise (DOX/EX) groups. Four weeks after intraperitoneal DOX injection (1mg/kg(-1)/d(-1); 10 days), shortening fraction in DOX/SED and DOX/EX was significantly reduced. Treadmill exercise was performed during 6 weeks, 5 days/week(-1), 30minutes/day(-1), 50% to 60% of maximum velocity. Survival was higher in DOX/EX (67%) than DOX/SED (33%). No differences were observed in intraplatelet L-arginine transport assessed by incubation with L- [(3)H]-arginine, nor in NOS activity measured by the conversion of L- [(3)H]-arginine into L- [(3)H]-citrulline among the groups. Vasodilation response to acetylcholine was impaired in DOX/SED and DOX/EX; in nitroglycerine, it was limited to DOX/SED. Aerobic training reduced mortality in DOX-induced HF animals and restored vascular smooth muscle relaxation properties. However, it did not ameliorate intraplatelet NO bioavailability and endothelial function during the period studied.

Hypertension and kidney alterations in rat offspring from low protein pregnancies.

OBJECTIVE: Low birth weight contributes to the early onset of end-stage renal disease. Therefore, this study was undertaken to investigate early and late glomerular structural alterations in both sexes of Wistar rat offspring from dams submitted to severe low protein intake during gestation. METHODS: Offspring from dams fed normal protein (19% of protein) or low protein (5% of protein) were studied at days 0, 10, 90 and 180 of age. RESULTS: Inner cortical structure showed immature (comma-shaped and S-shaped forms) and mature corpuscles in different proportions in low protein offspring (less maturity) and normal protein offspring (more maturity). At day 10 (end of the nephrogenesis period), immature corpuscles were observed only in low protein offspring. In adulthood, low protein offspring had higher blood pressure, and showed thicker glomerular basement membrane (GBM) with effacement of the pedicles, and slit diaphragm absent with some podocytes directly adhering to the basal membrane with pedicles absent. The number of renal corpuscles was lower in low protein offspring than in normal protein offspring of the same sex, all age groups (P < 0.001). No interaction was observed between sex and maternal nutrition for the same sex and all age groups. CONCLUSION: Gestational low protein leads to glomerulogenesis retardation and consequently a lower nephron number with thick GBM and structural alterations in the pedicles of podocytes.

Morphologic study of embryonic development of rat duodenum through a computerized three-dimensional reconstruction: critical analysis of solid core theory.

To date, intrinsic obstructions of the duodenum have been explained by the "solid core" theory, described by Tandler in 1902 (Morphol Jahrb 29:187-216, 1902). This study aimed to evaluate the epithelial occlusion of rat duodenum during embryonic development, through optical microscopy and computerized three-dimensional reconstruction. The Wistar rat embryos used in this study had 13, 14, 15, and 16 days of gestation. This corresponds to human embryos with 33, 40, 44, and 52 days of development, which is between the fifth and eighth week. The study included 12 embryos studied by optical microscopy, and four by three-dimensional reconstruction (those with 13, 14, 15, and 16 days). Through optical microscopy, an intense epithelial proliferation was observed in the gestation embryo of 13 days, with no occlusion of the opening of the duodenum. In the embryos with 14, 15, and 16 days of gestation, an increase in diameter of the duodenum was observed along with intestinal development. Through three-dimensional reconstruction, it was observed that the opening of the digestive tube of rat embryos with 13-16 days of gestation is never obstructed by epithelial proliferation, although it may follow a sinuous path. This study concludes that the "solid core" phase described by Tandler does not occur in the embryonic development of rat duodenum.