Global dynamics of discrete mathematical models of tuberculosis.

In this paper, we develop discrete models of Tuberculosis (TB). This includes SEI endogenous and exogenous models without treatment. These models are then extended to a SEIT model with treatment. We develop two types of net reproduction numbers, one is the traditional R0 which is based on the disease-free equilibrium, and a new net reproduction number R0(E∗) based on the endemic equilibrium. It is shown that the disease-free equilibrium is globally asymptotically stable if R0≤ 1 and unstable if R0>1. Moreover, the endemic equilibrium is locally asymptotically stable if R0(E∗)<1

Inferior oblique myectomy for postoperative limitation of elevation in abduction.

Antielevation syndrome is commonly described following anteriorization of the inferior oblique muscle. A similar phenomenon may occur following inferior oblique muscle recession, creating a distinct strabismus pattern in the setting of cranial trochlear nerve palsy. We report 3 adult patients, 69-72 years of age, who presented at the Stanford Byers Eye Institute with a similar strabismus pattern-limited elevation in abduction following previous inferior oblique muscle recession for congenital/long-standing trochlear nerve palsy. All 3 patients had a small hypertropia in primary gaze with ipsilateral inferior oblique overaction, limited elevation in abduction, and inferotemporal conjunctival scars. Two patients had a V-pattern strabismus. Following myectomy of the previously recessed inferior oblique muscle, elevation in abduction improved, and symptoms resolved in all 3 patients.

Comparative effects of finasteride and minoxidil on the male reproductive organs: A systematic review of in vitro and in vivo evidence.

Finasteride and minoxidil are medicaments commonly prescribed for treating benign prostatic hyperplasia (BPA), hypertension, and/or androgenetic alopecia (AGA). The mechanism of action of finasteride is based on the interference in androgenic pathways, which may lead to fertility-related disorders in men. Minoxidil, however, can act in multiple ways, and there is no consensus that its use can adversely affect male fertility. Since finasteride and minoxidil could be risk factors for male fertility, we aimed to compare their impact on the two reproductive organs testis and epididymis of adult murine models, besides testis/epididymis-related cells, and describe the mechanism of action involved. For such, we used the PRISMA guideline. We included 31 original studies from a structured search on PubMed/MEDLINE, Scopus, and Web of Science databases. For in vivo studies, the bias analysis and the quality of the studies were assessed as described by SYRCLE (Systematic Review Centre for Laboratory Animal Experimentation). We concluded that finasteride and minoxidil act as hormone disruptors, causing oxidative stress and morphological changes mainly in the testis. Our results also revealed that finasteride treatment could be more harmful to male reproductive health because it was more associated with reproductive injuries, including damage to the epididymis, erectile dysfunction, decreased libido, and reduced semen volume. Thus, this study contributes to the global understanding of the mechanisms by which medicaments used for alopecia might lead to male reproductive disorders. We hope that our critical analysis expedites clinical research and reduces methodological bias. The registration number on the Prospero platform is CRD42022313347.

Toxicology of arsenate, arsenite, cadmium, lead, chromium, and nickel in testes of adult Swiss mice after chronic exposure by intraperitoneal route.

BACKGROUND: Some residues such as the heavy metals cadmium (Cd), lead (Pb), chromium (Cr VI), nickel (Ni), and arsenic (As), this last one in its oxidized forms + 5 (arsenate) and + 3 (arsenite), can cause injuries to human health, so they are currently considered environmental health emergencies. In the testis, heavy metals can cause morphological and functional damage due to constant exposure acting chronically in individuals. Thus, we aimed to determine the toxicological mechanism of As+5, As+3, Cd, Cr VI, and Ni that leads to testicular damage and establish for the first time an order of toxicity among these studied heavy metals. METHODS: Forty-two Swiss mice at reproductive age (140 days) were used, randomly distributed into seven experimental groups (n = 6). Exposure to heavy metals was weekly performed, by intraperitoneal route. Group 1 received 0.7 mL 0.9% saline (control), and the other groups received 1.5 mg/ kg of As+5, As+3, Cd, Pb, Cr VI, or Ni, for six weeks. RESULTS: These studied heavy metals did not accumulate in the testis tissue. However, exposure to Ni induced moderate pathologies in the seminiferous tubules, plus changes in the tunica propria, blood vessels, lymphatic space, and carbonyl protein levels. Cd exposure caused moderate tubular histopathologies and changes in the blood vessels and lymphatic space. Cr VI induced slight tubular histopathologies, changes in the lymphatic space, blood vessels, and SOD activity. Pb and As+3 exposure triggered moderate tubular pathologies and changes in the SOD activity and carbonyl protein levels, respectively. Finally, As+5 induced only slight tubular pathologies. CONCLUSION: The testicular histopathologies caused by the studied heavy metals are mainly triggered by changes in testicular oxidative balance. Based on our findings of histomorphological alterations, the toxicity order among the heavy metals is Ni>Cd>Cr(VI)>PbAs+3 >As+5. However, considering oxidative stress results, we propose the following testicular toxicity order for these heavy metals: Ni>As+3 > Cd>Cr(VI)>Pb>As+5. Ni exposure shows the most harmful among the heavy metals to the testis.

Anterior segment ischemia following strabismus surgery in a young adult using gender-affirming estrogen hormone therapy.

Well-known risk factors for anterior segment ischemia (ASI) following strabismus surgery include ipsilateral surgery on three or more rectus muscles, older age, and vasculopathy. ASI is rarely reported in young patients following uneventful strabismus surgery on two ipsilateral rectus muscles. We report a 30-year-old transgender female on long-term estrogen therapy who underwent strabismus surgery involving recessions of both lateral rectus muscles, the right inferior rectus muscle, and the left superior rectus muscle. The left eye developed severe ASI with hypotony maculopathy that was resistant to topical medications, oral steroids, anterior chamber reformation, and intravitreal steroid injection. Following phacoemulsification with intraocular lens and capsular tension ring insertion 1 year later, intraocular pressure and hypotony maculopathy improved.

Direct imaging and astrometric detection of a gas giant planet orbiting an accelerating star.

Direct imaging of gas giant exoplanets provides information on their atmospheres and the architectures of planetary systems. However, few planets have been detected in blind surveys with direct imaging. Using astrometry from the Gaia and Hipparcos spacecraft, we identified dynamical evidence for a gas giant planet around the nearby star HIP 99770. We confirmed the detection of this planet with direct imaging using the Subaru Coronagraphic Extreme Adaptive Optics instrument. The planet, HIP 99770 b, orbits 17 astronomical units from its host star, receiving an amount of light similar to that reaching Jupiter. Its dynamical mass is 13.9 to 16.1 Jupiter masses. The planet-to-star mass ratio [(7 to 8) × 10-3] is similar to that of other directly imaged planets. The planet's atmospheric spectrum indicates an older, less cloudy analog of the previously imaged exoplanets around HR 8799.

Septin-5 and -7-IgGs: Neurologic, Serologic, and Pathophysiologic Characteristics.

BACKGROUND AND OBJECTIVES: We sought to determine clinical significance of neuronal septin autoimmunity and evaluate for potential IgG effects. METHODS: Septin-IgGs were detected by indirect immunofluorescence assays (IFAs; mouse tissue and cell based) or Western blot. IgG binding to (and internalization of) extracellular septin epitopes were evaluated for by live rat hippocampal neuron assay. The impact of purified patient IgGs on murine cortical neuron function was determined by recording extracellular field potentials in a multielectrode array platform. RESULTS: Septin-IgGs were identified in 23 patients. All 8 patients with septin-5-IgG detected had cerebellar ataxia, and 7 had prominent eye movement disorders. One of 2 patients with co-existing septin-7-IgG had additional psychiatric phenotype (apathy, emotional blunting, and poor insight). Fifteen patients had septin-7 autoimmunity, without septin-5-IgG detected. Disorders included encephalopathy (11; 2 patients with accompanying myelopathy, and 2 were relapsing), myelopathy (3), and episodic ataxia (1). Psychiatric symptoms (≥1 of agitation, apathy, catatonia, disorganized thinking, and paranoia) were prominent in 6 of 11 patients with encephalopathic symptoms. Eight of 10 patients with data available (from 23 total) improved after immunotherapy, and a further 2 patients improved spontaneously. Staining of plasma membranes of live hippocampal neurons produced by patient IgGs (subclasses 1 and 2) colocalized with pre- and post-synaptic markers. Decreased spiking and bursting behavior in mixed cultures of murine glutamatergic and GABAergic cortical neurons produced by patient IgGs were attributable to neither antigenic crosslinking and internalization nor complement activation. INTERPRETATION: Septin-IgGs are predictive of distinct treatment-responsive autoimmune central nervous system (CNS) disorders. Live neuron binding and induced electrophysiologic effects by patient IgGs may support septin-specific pathophysiology. ANN NEUROL 2022;92:1090-1101.

Outcomes of inferonasal glaucoma drainage device surgery in the management of childhood glaucoma.

PURPOSE: To evaluate indications and postoperative outcomes of inferonasal Ahmed and Baerveldt glaucoma drainage devices (GDDs) in pediatric glaucoma. METHODS: This retrospective study included patients ≤18 years of age at inferonasal GDD placement, from June 2013 to September 2021. Demographic information, indications, and outcomes were recorded. Successful eyes had intraocular pressure (IOP) ≥5 and ≤21 mm Hg or (in severe cases, where entry IOP was ≤21 mm Hg) 20% below preoperative values without additional IOP-lowering surgery or vision-threatening complications. RESULTS: A total of 68 eyes of 52 patients were included. Mean age was 9.8 ± 5.8 years. Most common diagnoses included primary congenital glaucoma (n = 28 eyes [41%]) and glaucoma following cataract surgery (n = 12 eyes [18%]). Success rates by Kaplan-Meier survival analysis (95% CI) at 1, 2, 3, and 5 years were 62.2% (49.4-72.7), 49.0% (36.3-60.6), 36.8% (24.0-49.8), and 31.9% (18.5-44.5), respectively. Surgical failure was associated with Ahmed (vs Baerveldt) GDD (HR = 3.2; P = 0.002) and inferonasal site as initial (vs subsequent) GDD received (HR = 2.2; P = 0.048). Twenty-five eyes (36.7%) had at least one complication. Although vision-threatening complications were uncommon (n = 2 eyes [3%]), less severe complications were relatively common and included new/worsened strabismus (n = 9 patients [17%]), corneal edema (n = 6 eyes [9%]), lens opacities (n = 4 [6%]), tube or patch graft exposure (n = 3 [4%]), tube blockage (n = 2 eyes [3%]), and other (n = 8 eyes [12%]). CONCLUSIONS: In this study cohort, inferonasal GDDs for childhood glaucoma had modest success, with frequent though rarely vision-threatening complications.

Efficacy and Safety of Subcutaneous Esketamine in the Treatment of Suicidality in Major Depressive Disorder and Bipolar Depression.

BACKGROUND AND OBJECTIVE: Affective disorders account for most cases of suicide. The pharmacological arsenal to treat suicidality is limited and available agents take too long to take effect. A large body of evidence shows optimal results of ketamine for treating depression, but the evidence concerning suicidality has not been fully described. We report the first real-world study of severely depressed patients presenting with suicide ideation who were treated with repeated administration of subcutaneous esketamine. METHODS: We analyzed data from 70 acutely depressed subjects diagnosed with resistant major depressive disorder or bipolar depression. Subjects were administered subcutaneous esketamine once a week for 6 weeks. The primary efficacy endpoint, the change from baseline to 24-h post-administration 6 in the item 10 Montgomery-Åsberg Depression Rating Scale score, was analyzed using a mixed-effects repeated-measures model. RESULTS: There were significant effects for time on item 10 Montgomery-Åsberg Depression Rating Scale scores (p < 0.0001) but not for a time × diagnosis interaction (p = 0.164) from baseline to the end of the study. Efficacy of esketamine did not differ between groups (major depressive disorder vs bipolar depression) at any timepoint. Statistical significance on suicidality scores was observed from 24 h after the first administration (p < 0.001), and a further reduction was observed with repeated administrations. Esketamine was safe and well tolerated. Mean heart rate remained stable during the administrations and the blood pressure increase was self-limited. CONCLUSIONS: Repeated subcutaneous esketamine administration had significant anti-suicidality effects in both major depressive disorder and bipolar groups, with a rapid onset of action and a good tolerability profile. Large randomized controlled trials are warranted to confirm these preliminary findings.

Mem-fractive properties of mushrooms.

Memristors close the loop forI-Vcharacteristics of the traditional, passive, semi-conductor devices. A memristor is a physical realisation of the material implication and thus is a universal logical element. Memristors are getting particular interest in the field of bioelectronics. Electrical properties of living substrates are not binary and there is nearly a continuous transitions from being non-memristive to mem-fractive (exhibiting a combination of passive memory) to ideally memristive. In laboratory experiments we show that living oyster mushroomsPleurotus ostreatusexhibit mem-fractive properties. We offer a piece-wise polynomial approximation of theI-Vbehaviour of the oyster mushrooms. We also report spiking activity, oscillations in conduced current of the oyster mushrooms.

Granulicatella Adiacens as an Unusual Cause of Microbial Keratitis and Endophthalmitis: A Case Series and Literature Review.

PURPOSE: To report two cases of microbial keratitis and/or endophthalmitis involving Granulicatella adiacens. METHODS: Case series. RESULTS: 24-year-old female with a history of Herpes simplex virus 1 (HSV-1) and Candida parapsilosis keratitis presented with a geographic epithelial defect and infiltrate in the left eye. Cultures were positive for HSV-1 and G. adiacens. Keratitis resolved with topical vancomycin and oral valacyclovir. A 65-year-old female with a history of type II diabetes and failed therapeutic penetrating keratoplasty presented with inferior corneal graft haze and vitreous inflammation of the right eye. Therapeutic penetrating keratoplasty and pars plana vitrectomy were performed, and the corneal button returned positive for G. adiacens. The patient was treated with topical and intravitreal vancomycin as well as topical and systemic steroids. CONCLUSIONS: These cases expand the literature on G. adiacens keratitis and endophthalmitis and corroborate the role of steroid use and prior surgery as paramount risk factors.

Percutaneous flexor digitorum brevis tenotomy: An anatomical study.

INTRODUCTION: A percutaneous selective flexor digitorum brevis (FDB) tenotomy and a proximal interphalangeal (PIP) joint arthrolysis may correct a lesser claw toe deformity keeping flexor digitorum longus (FDL) and active flexion. Our study aimed to verify if the procedure was effective and reliable and if it respects the surrounding soft tissues. MATERIAL AND METHOD: Twelve cadaveric lateral toes were used. A dissection ensured the integrity of both digital nerves, FDL and flexor pulleys and assessed the section of both FDB slips and PIP arthrolysis. RESULTS: A complete section of the two FDB slips was observed in 4 cases (33%). Arthrolysis was achieved in all cases. Surrounding soft tissues were found intact in all cases. CONCLUSION: This procedure is effective regarding PIP arthrolysis, but a technical improvement is required to achieve a reliable section of both FDB slips. In the hands of an experienced surgeon, it has proven to be safe.

Phase 2 Trial of Rituximab in Acetylcholine Receptor Antibody-Positive Generalized Myasthenia Gravis: The BeatMG Study.

OBJECTIVE: To determine whether rituximab is safe and potentially beneficial, warranting further investigation in an efficacy trial for acetylcholine receptor antibody-positive generalized MG (AChR-Ab+ gMG). METHODS: The B-Cell Targeted Treatment in MG (BeatMG) study was a randomized, double-blind, placebo-controlled, multicenter phase-2 trial that utilized a futility design. Individuals 21-90 years of age, with AChR-Ab+ gMG (MG Foundation of America Class II-IV) and receiving prednisone ≥15 mg/day were eligible. The primary outcome was a measure of steroid-sparing effect, defined as the proportion achieving ≥75% reduction in mean daily prednisone dose in the 4-weeks prior to week 52 and with clinical improvement or no significant worsening as compared to the 4-week period prior to randomization. The co-primary outcome was safety. Secondary outcomes included MG-specific clinical assessments. Fifty-two individuals were randomized (1:1) to either a two-cycle rituximab/placebo regimen, with follow-up through 52-weeks. RESULTS: Of the 52 participants included, mean (±SD) age at enrollment was 55.1 (±17.1) years; 23 (44.2%) were female, and 31 (59.6%) were MGFA Class II. The mean (±SD) baseline prednisone dose was 22.1 (±9.7) mg/day. The primary steroid-sparing outcome was achieved in 60% of those on rituximab vs. 56% on placebo. The study reached its futility endpoint (p=0.03) suggesting that the pre-defined clinically meaningful improvement of 30% due to rituximab over placebo was unlikely to be achieved in a subsequent, larger trial. No safety issues identified. CONCLUSIONS: While rituximab was safe and well-tolerated, these results suggest that there is a low probability of observing the defined clinically meaningful steroid-sparing effect over a 12-month period in a phase-3 trial of mild-moderately symptomatic AChR-Ab+ gMG. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for mild-to-moderate AChR-Ab+ gMG, compared with placebo, rituximab is safe but unlikely to reduce steroid use by an absolute difference of at least 30% at 1 year. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02110706.

Some elements for a history of the dynamical systems theory.

Writing a history of a scientific theory is always difficult because it requires to focus on some key contributors and to "reconstruct" some supposed influences. In the 1970s, a new way of performing science under the name "chaos" emerged, combining the mathematics from the nonlinear dynamical systems theory and numerical simulations. To provide a direct testimony of how contributors can be influenced by other scientists or works, we here collected some writings about the early times of a few contributors to chaos theory. The purpose is to exhibit the diversity in the paths and to bring some elements-which were never published-illustrating the atmosphere of this period. Some peculiarities of chaos theory are also discussed.

Vector-apodizing phase plate coronagraph: design, current performance, and future development [Invited].

Over the last decade, the vector-apodizing phase plate (vAPP) coronagraph has been developed from concept to on-sky application in many high-contrast imaging systems on 8 m class telescopes. The vAPP is a geometric-phase patterned coronagraph that is inherently broadband, and its manufacturing is enabled only by direct-write technology for liquid-crystal patterns. The vAPP generates two coronagraphic point spread functions (PSFs) that cancel starlight on opposite sides of the PSF and have opposite circular polarization states. The efficiency, that is, the amount of light in these PSFs, depends on the retardance offset from a half-wave of the liquid-crystal retarder. Using different liquid-crystal recipes to tune the retardance, different vAPPs operate with high efficiencies (${\gt}96\%$) in the visible and thermal infrared (0.55 µm to 5 µm). Since 2015, seven vAPPs have been installed in a total of six different instruments, including Magellan/MagAO, Magellan/MagAO-X, Subaru/SCExAO, and LBT/LMIRcam. Using two integral field spectrographs installed on the latter two instruments, these vAPPs can provide low-resolution spectra (${\rm{R}} \sim 30$) between 1 µm and 5 µm. We review the design process, development, commissioning, on-sky performance, and first scientific results of all commissioned vAPPs. We report on the lessons learned and conclude with perspectives for future developments and applications.

3D-M3: high-spatial-resolution spectroscopy with extreme AO and 3D-printed micro-lenslets.

By combining integral field spectroscopy with extreme adaptive optics, we are now able to resolve objects close to the diffraction limit of large telescopes, exploring new science cases. We introduce an integral field unit designed to couple light with a minimal plate scale from the SCExAO facility at NIR wavelengths to a single-mode spectrograph. The integral field unit has a 3D-printed micro-lens array on top of a custom single-mode multi-core fiber, to optimize the coupling of light into the fiber cores. We demonstrate the potential of the instrument via initial results from the first on-sky runs at the 8.2 m Subaru Telescope with a spectrograph using off-the-shelf optics, allowing for rapid development with low cost.

Scalable photonic-based nulling interferometry with the dispersed multi-baseline GLINT instrument.

Characterisation of exoplanets is key to understanding their formation, composition and potential for life. Nulling interferometry, combined with extreme adaptive optics, is among the most promising techniques to advance this goal. We present an integrated-optic nuller whose design is directly scalable to future science-ready interferometric nullers: the Guided-Light Interferometric Nulling Technology, deployed at the Subaru Telescope. It combines four beams and delivers spatial and spectral information. We demonstrate the capability of the instrument, achieving a null depth better than 10-3 with a precision of 10-4 for all baselines, in laboratory conditions with simulated seeing applied. On sky, the instrument delivered angular diameter measurements of stars that were 2.5 times smaller than the diffraction limit of the telescope. These successes pave the way for future design enhancements: scaling to more baselines, improved photonic component and handling low-order atmospheric aberration within the instrument, all of which will contribute to enhance sensitivity and precision.

Lumbosacral plexopathy due to pelvic hematoma after extracorporeal membrane oxygenation: A case report.

RATIONALE: Peripheral nerve injury related to vascular complications associated with extracorporeal membrane oxygenation (ECMO) is perhaps underappreciated. Compared to the well-described central nervous system complications of ECMO, brachial plexopathy and lumbosacral plexopathy have rarely been reported. We report this case to heighten awareness of lumbosacral plexus injury due to pelvic hematoma formation after ECMO. PATIENT CONCERNS: A 53-year-old woman developed a large pelvic hematoma with significant mass effect on intrapelvic structures after receiving lifesaving venoarterial ECMO for cardiogenic shock following a cardiac arrest. During her hospital course, she developed bilateral foot drop that was attributed to critical illness. Her lack of neurological recovery after 6 months prompted referral to neuromuscular medicine for consultation. DIAGNOSIS: The patient was retrospectively diagnosed with bilateral lumbosacral plexopathy due to the large pelvic hematoma. INTERVENTION: Electromyography/nerve conduction study (EMG/NCS) obtained at the time of referral to neuromuscular medicine localized her neurological deficits to the bilateral lumbosacral plexus and demonstrated no volitional motor unit action potentials in her lower leg muscles. OUTCOMES: The patient had minimal recovery of strength at the level of the ankles but was ambulatory with solid ankle-foot orthoses due to spared proximal lower extremity strength. Unfortunately, the absence of any volitionally activated motor unit action potentials in her lower leg muscles on EMG performed 6 months after the initial injury was a poor prognostic indicator for successful reinnervation and future neurological recovery. LESSONS: Neurological deficits occurring during the course of administration of ECMO require accurate localization. Neurology consultation and/or EMG/NCS may be useful if localization is not clear. Lesions localizing to the lumbosacral plexus should prompt radiographic evaluation with computed tomography of the abdomen and pelvis. Hemostasis of a retroperitoneal hematoma may be achieved with embolization. However, if neurological deficits do not improve, surgical consultation for hematoma evacuation may be warranted.

Relevance of the Isoflavone Absorption and Testicular Function: A Systematic Review of Preclinical Evidence.

Isoflavone is a phytoestrogen found in different types of food that can act as endocrine disrupters leading to testicular dysfunction. Currently, fragmented data on the action of this compound in the testicles make it difficult to assess its effects to define a safe dose. Thus, we systematically reviewed the preclinical evidence of the impact of isoflavone on testicular function. We also determined which form (aglycones or glycosylated) was the most used, which allowed us to understand the main biological processes involved in testicular function after isoflavone exposure. This systematic review was carried out according to the PRISMA guidelines using a structured search on the biomedical databases MEDLINE (PubMed), Scopus, and Web of Science, recovering and analyzing 22 original studies. The bias analysis and the quality of the studies were assessed by the criteria described in the risk of bias tool developed by SYRCLE (Systematic Review Centre for Laboratory Animal Experimentation). The aglycones and glycosylated isoflavones proved to be harmful to the reproductive health, and the glycosylates at doses of 50, 100, 146, 200, 300, 500, and 600 mg/kg, in addition to 190 and 1000 mg/L, appear to be even more harmful. The main testicular pathologies resulting from the use of isoflavones are associated with Leydig cells resulting from changes in molecular functions and cellular components. The most used isoflavone to evaluate testicular changes was the genistein/daidzein conjugate. The consumption of high doses of isoflavones promotes changes in the functioning of Leydig cells, inducing testicular changes and leading to infertility in murine models.

Different Routes of Administration Lead to Different Oxidative Damage and Tissue Disorganization Levels on the Subacute Cadmium Toxicity in the Liver.

The toxic effects of cadmium (Cd) on hepatic parameters are widely described in the literature. Experimental models often make use of the intraperitoneal route (i.p.) because it is easier to apply, while in the oral route, Cd poisoning in humans is best represented by allowing the metal to pass through the digestive system and be absorbed into the bloodstream. Thus, this study investigated the Cd exposure impact on the liver, by comparing both i.p. and oral routes, both in single dose, in addition to the oral route in fractional doses. Swiss adult male mice received CdCl2 1.5 mg/kg i.p., 30 mg/kg oral single dose, and 4.28 mg/kg oral route in fractional doses for 7 consecutive days. Cd bioaccumulation was observed in all animals exposed to Cd. Hepatic concentrations of Ca and Fe increased only in the fractionated oral route. Liver activities of SOD and CAT increased only by oral single dose. GST decreased in all forms of oral administration, while MDA decreased only in i.p. route. Liver weight and HSI increased in the i.p. route, while organ volume increased in all forms of oral administration, and liver density increased in all animals exposed to Cd. In hepatic histomorphometry, the changes were more evident in oral administration, mainly in exposure to metal in a single dose. Thus, the subacute administration of Cd in different routes of administration leads to different changes in liver poisoning.